Updated on 2024/05/01

写真a

 
Ayako Wakabayashi
 
Affiliation
Faculty of Medicine, Department of Microbiology and Immunology, Senior Assistant Professor
Title
Senior Assistant Professor
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Degree

  • Ph.D ( Tokyo Medical and Dental University )

Research Interests

  • Immunology

  • allergy

  • Mucosal Immunology

  • Food Hygiene

  • gut microbiome

Research Areas

  • Life Science / Immunology

Research History

  • Nippon Medical School   Department of Microbiology and Immunology   Senior Assistant Professor

    2016

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  • Nippon Medical School   Department of Microbiology and Immunology   Assistant Professor

    2007 - 2016

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  • Japan Women's University   Adjunct Asistant Professor

    2001

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  • Nippon Medical School   Department of Microbiology and Immunology   Research Associate

    1999 - 2007

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  • Japan Foundation for Aging and Health   Research Resident

    1997 - 1999

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  • Nippon Medical School

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  • Nippon Medical School Department of Microbiology and Immunology   Senior Assistant Professor

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Professional Memberships

  • THE JAPANESE SOCIETY FOR IMMUNOLOGY

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  • JAPAN SOCIETY OF NUTRITION AND FOOD SCIENCE

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  • JAPANESE SOCIETY OF ALLERGOLOGY

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Committee Memberships

  • 学校法人日本医科大学しあわせキャリア支援センター   委員  

    2019.4   

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  • 日本医科大学法人本部女性医師・研究者支援室   室員  

    2015.4 - 2019.3   

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Papers

  • HMGB1 released from intestinal epithelia damaged by cholera toxin adjuvant contributes to activation of mucosal dendritic cells and induction of intestinal cytotoxic T lymphocytes and IgA. Reviewed International journal

    Ayako Wakabayashi, Masumi Shimizu, Eiji Shinya, Hidemi Takahashi

    Cell death & disease   9 ( 6 )   631 - 631   2018.5

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Nature Publishing Group  

    Cholera toxin (CT) is a potent mucosal adjuvant and oral administration of ovalbumin (OVA) antigens plus CT induces OVA-specific CD8+ cytotoxic T lymphocytes (CTLs) and IgA production in intestinal mucosa. However, the mechanisms of induction of these immune responses remain unknown. Intestinal OVA-specific CD8+ CTLs were not induced by oral administration of the CT active (CTA) or CT binding (CTB) subunit as an adjuvant and CD11c+ DCs were involved in cross-priming of intestinal CTLs. CD8+CD103+CD11c+CD11b-DCs and DCIR2+CD103+CD11c+CD11b+ DCs were distributed in the intestinal lamina propria and mesenteric lymph nodes, both DC subsets expressed DEC-205, and the expression of co-stimulatory molecules such as CD80 and CD86 was enhanced in both DC subsets after oral administration of intact CT but not the CTA or CTB subunit. Intestinal DCs activated by the oral administration of OVA plus CT cross-presented OVA antigens and DCs that captured OVA antigen through DEC-205, but not DCIR2, could cross-present antigen. We found that oral administration of intact CT, but not the CTA or CTB subunit, enhanced cell death, cytoplasmic expression of high-mobility group box 1 protein (HMGB1) in epithelial cell adhesion molecule (EpCAM)+CD45- intestinal epithelial cells (IECs), and HMGB1 levels in fecal extracts. HMGB1 dose-dependently enhanced the expression of CD80 and CD86 on DCs in vitro, and intravenous or oral administration of glycyrrhizin, an HMGB1 inhibitor, significantly suppressed activation of mucosal DCs and induction of intestinal OVA-specific CTLs and IgA by oral CT administration. These results showed that oral administration of intact CT triggers epithelial cell death in the gut and the release of HMGB1 from damaged IECs, and that the released HMGB1 may mediate activation of mucosal DCs and induction of CTLs and IgA in the intestine.

    DOI： 10.1038/s41419-018-0665-z

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  • Effects of Dendritic Cell Subset Manipulation on Airway Allergy in a Mouse Model. Reviewed International journal

    Ryosuke Murakami, Yohko Nakagawa, Masumi Shimizu, Ayako Wakabayashi, Yasuyuki Negishi, Takachika Hiroi, Kimihiro Okubo, Hidemi Takahashi

    International archives of allergy and immunology   168 ( 4 )   219 - 32   2015

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

    Background: Two major distinct subsets of dendritic cells (DCs) are arranged to regulate immune responses: DEC-205+ DCs drive Th1 polarization and 33D1+ DCs establish Th2 dominancy. Th1 polarization can be achieved either by depletion of 33D1+ DCs with a 33D1-specific monoclonal antibody (mAb) or by activation of DEC-205+ DCs via intraperitoneal injection of alpha-galactosylceramide (alpha-GalCer). We studied the effect of 33D1+ DC depletion or DEC-205+ DC activation in vivo using an established mouse model of allergic rhinitis (AR). Methods: Mice were injected intraperitoneally with OVA plus alum and challenged 4 times with daily intranasal administration of OVA. Immediately after the last challenge, allergic symptoms such as sneezing and nasal rubbing as well as the number of cells in the bronchoalveolar lavage fluid (BALF) and nasal lavage fluid (NALF) were counted. The levels of serum OVA-specific IgG1, IgG2a, and IgE were also determined by ELISA. Results: The allergic symptom scores were significantly decreased in 33D1+ DC-depleted or DEC-205+ DC-activated AR mice. The levels of OVA-specific IgG1, IgG2a, and IgE, and the number of NALF cells, but not BALF cells, were reduced in 33D1+ DC-depleted but not in DEC-205+ DC-activated AR mice. Moreover, the activated DEC-205+ DCs suppressed histamine release from IgE-sensitized mast cells, probably through IL-12 secretion. Conclusions: The manipulation of innate DC subsets may provide a new therapeutic strategy for controlling various allergic diseases by reducing histamine release from IgE-sensitized mast cells by driving the immune response towards Th1 dominancy via activation of DEC-205+ DCs in vivo. (C) 2016 The Author(s) Published by S. Karger AG, Basel

    DOI： 10.1159/000443237

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  • Inactivation of tumor-specific CD8⁺ CTLs by tumor-infiltrating tolerogenic dendritic cells. Reviewed International journal

    Hirotomo Harimoto, Masumi Shimizu, Yohko Nakagawa, Katsuhisa Nakatsuka, Ayako Wakabayashi, Choitsu Sakamoto, Hidemi Takahashi

    Immunology and cell biology   91 ( 9 )   545 - 55   2013.10

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

    Cancer immunosurveillance failure is largely attributed to the insufficient activation of tumor-specific class I major histocompatibility complex (MHC) molecule (MHC-I)-restricted CD8(+) cytotoxic T lymphocytes (CTLs). DEC-205(+) dendritic cells (DCs), having the ability to cross-present, can present captured tumor antigens on MHC-I alongside costimulatory molecules, inducing the priming and activation of tumor-specific CD8(+) CTLs. It has been suggested that reduced levels of costimulatory molecules on DCs may be a cause of impaired CTL induction and that some tumors may induce the downregulation of costimulatory molecules on tolerogenic DCs. To examine such possibilities, we established two distinct types of murine hepatoma cell lines, named Hepa1-6-1 and Hepa1-6-2 (derived from Hepa1-6 cells), and confirmed that they display similar antigenicities, as well as identical surface expression of MHC-I. We found that Hepa1-6-1 had the ability to grow continuously after subcutaneous implantation into syngeneic C57BL/6 mice and did not prime CD8(+) CTLs. In contrast, Hepa1-6-2 cells, which display reduced levels of adhesion molecules, such as Intercellular Adhesion Molecule 1 (ICAM-1), failed to grow in vivo and efficiently primed CTLs. Moreover, Hepa1-6-1-derived factors, such as transforming growth factor (TGF)-beta 1, vascular endothelial growth factor (VEGF) and a-fetoprotein (AFP), converted CD11chigh MHC-IIhigh DEC-205(+) DC subsets into tolerogenic cells, displaying downregulated costimulatory molecules and having impaired cross-presenting capacities. These immunosuppressive tolerogenic DCs appeared to inhibit the induction of tumor-specific CD8(+) CTLs and suppress their cytotoxic functions within the tumor. Together, the findings presented here provide a new method of cancer immunotherapy using the selective suppression, depletion or alteration of immunosuppressive tolerogenic DCs within tumors.

    DOI： 10.1038/icb.2013.38

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  • Disruption of maternal immune balance maintained by innate DC subsets results in spontaneous pregnancy loss in mice. Reviewed International journal

    Yasuyuki Negishi, Ayako Wakabayashi, Masumi Shimizu, Tomoko Ichikawa, Yoshihiro Kumagai, Toshiyuki Takeshita, Hidemi Takahashi

    Immunobiology   217 ( 10 )   951 - 61   2012.10

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER GMBH, URBAN & FISCHER VERLAG  

    Dendritic cells (DCs) play an important role in providing an appropriate fetal/maternal balance between Th1 and Th2 during pregnancy. The Th1/Th2 balance seems to be regulated mainly by two distinct DC subsets, DEC-205(+) DCs having the capacity to establish Th1 polarization and 33D1(+) DCs to induce Th2 dominance. Pregnancy is established and maintained by maternal hormones, such as progesterone and estrogen, and the balance of DC subtypes was affected mainly by progesterone, which induced a dose-dependent reduction of the DEC-205/33D1 ratio together with/without a stable amount of estrogen. The DEC-205/33D1 ratio decreased gradually with the progress of pregnancy and rapid augmentation of the ratio was seen around delivery in vivo. Here, we demonstrate that depletion of 33D1(+) DCs during the perinatal period caused substantial fetal loss probably mediated through Th1 up-regulation via transient IL-12 secretion, and pre-administration of progesterone could rescue the fetal loss. Similar miscarriages were also observed when pregnant mice were intraperitoneally (i.p.) injected twice with IL-12 on Gd 9.5 and 10.5. Moreover, prior inoculation of progesterone suppressed the enhanced serum IL-12 production in mice treated with 33D1 antibody, indicating that progesterone might inhibit temporal IL-12 secretion around Gd 10.5 and miscarriage was avoided. These findings suggest the importance of balancing DC subsets during pregnancy and reveal that we can avoid miscarriage by manipulating the activity of the DC subpopulation of pregnant individuals with maternal hormones. (c) 2012 Elsevier GmbH. All rights reserved.

    DOI： 10.1016/j.imbio.2012.01.011

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  • Induction of tumor-specific acquired immunity against already established tumors by selective stimulation of innate DEC-205(+) dendritic cells. Reviewed International journal

    Keiichi Moriya, Ayako Wakabayashi, Masumi Shimizu, Hideto Tamura, Kazuo Dan, Hidemi Takahashi

    Cancer immunology, immunotherapy : CII   59 ( 7 )   1083 - 95   2010.7

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

    Two major distinct subsets of dendritic cells (DCs) are arranged to regulate our immune responses in vivo; 33D1(+) and DEC-205(+) DCs. Using anti-33D1-specific monoclonal antibody, 33D1(+) DCs were successfully depleted from C57BL/6 mice. When 33D1(+) DC-depleted mice were stimulated with LPS, serum IL-12, but not IL-10 secretion that may be mediated by the remaining DEC-205(+) DCs was markedly enhanced, which may induce Th1 dominancy upon TLR signaling. The 33D1(+) DC-depleted mice, implanted with syngeneic Hepa1-6 hepatoma or B16-F10 melanoma cells into the dermis, showed apparent inhibition of already established tumor growth in vivo when they were subcutaneously (sc) injected once or twice with LPS after tumor implantation. Moreover, the development of lung metastasis of B16-F10 melanoma cells injected intravenously was also suppressed when 33D1(+) DC-deleted mice were stimulated twice with LPS in a similar manner, in which the actual cell number of NK1.1(+)CD3(-) NK cells in lung tissues was markedly increased. Furthermore, intraperitoneal (ip) administration of a very small amount of melphalan (l-phenylalanine mustard; l-PAM) (0.25 mg/kg) in LPS-stimulated 33D1(+) DC-deleted mice helped to induce H-2K(b)-restricted epitope-specific CD8(+) cytotoxic T lymphocytes (CTLs) among tumor-infiltrating lymphocytes against already established syngeneic E.G7-OVA lymphoma. These findings indicate the importance and effectiveness of selective targeting of a specific subset of DCs, such as DEC-205(+) DCs alone or with a very small amount of anticancer drugs to activate both CD8(+) CTLs and NK effectors without externally added tumor antigen stimulation in vivo and provide a new direction for tumor immunotherapy.

    DOI： 10.1007/s00262-010-0835-z

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  • Suppression of an already established tumor growing through activated mucosal CTLs induced by oral administration of tumor antigen with cholera toxin. Reviewed International journal

    Ayako Wakabayashi, Yohko Nakagawa, Masumi Shimizu, Keiichi Moriya, Yasuhiro Nishiyama, Hidemi Takahashi

    Journal of immunology (Baltimore, Md. : 1950)   180 ( 6 )   4000 - 10   2008.3

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC IMMUNOLOGISTS  

    Priming of CTLs at mucosal sites, where various tumors are originated, seems critical for controlling tumors. In the present study, the effect of the oral administration of OVA plus adjuvant cholera toxin (CT) on the induction of Ag-specific mucosal CTLs as well as their effect on tumor regression was investigated. Although OVA-specific TCRs expressing lymphocytes requiring in vitro restimulation to gain specific cytotoxicity could be detected by OVA peptide-bearing tetramers in both freshly isolated intraepithelial lymphocytes and spleen cells when OVA was orally administered CT, those showing direct cytotoxic activity without requiring in vitro restimulation were dominantly observed in intraepithelial lymphocytes. The magnitude of such direct cytotoxicity at mucosal sites was drastically enhanced after the second oral administration of OVA with intact whole CT but not with its subcomponent, an A subunit (CTA) or a B subunit (CTB). When OVA plus CT were orally administrated to C57BL/6 mice bearing OVA-expressing syngeneic tumor cells, E.G7-OVA, in either gastric tissue or the dermis, tumor growth was significantly suppressed after the second oral treatment; however, s.c. or i.p. injection of OVA plus CT did not show any remarkable suppression. Those mucosal OVA-specific CTLs having direct cytotoxicity expressed CD8 alpha beta but not CD8 alpha alpha, suggesting that they originated from thymus-educated cells. Moreover, the infiltration of such OVA-specific CD8(+) CTLs was observed in suppressed tumor tissues. These results indicate that the growth of ongoing tumor cells can be suppressed by activated CD8 alpha beta CTLs with tumor-specific cytotoxicity via an orally administered tumor Ag with a suitable mucosal adjuvant.

    DOI： 10.4049/jimmunol.180.6.4000

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  • Importance of gastrointestinal ingestion and macromolecular antigens in the vein for oral tolerance induction. Reviewed International journal

    Ayako Wakabayashi, Yoshihiro Kumagai, Eiji Watari, Masumi Shimizu, Masanori Utsuyama, Katsuiku Hirokawa, Hidemi Takahashi

    Immunology   119 ( 2 )   167 - 77   2006.10

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING  

    Oral administration of a certain dose of antigen can generally induce immunological tolerance against the same antigen. In this study, we showed the temporal appearance of ovalbumin (OVA) antigens in both portal and peripheral blood of mice after the oral administration of OVA. Furthermore, we detected 45 000 MW OVA in mouse serum 30 min after the oral administration of OVA. Based on this observation, we examined whether the injection of intact OVA into the portal or peripheral vein induces immunological tolerance against OVA. We found that the intravenous injection of intact OVA did not induce immunological tolerance but rather enhanced OVA-specific antibody production in some subclasses, suggesting that OVA antigens via the gastrointestinal tract but not intact OVA may contribute to establish immunological tolerance against OVA. Therefore, we examined the effects of digesting intact OVA in the gastrointestinal tract on the induction of oral tolerance. When mice were orally administered or injected into various gastrointestinal organs, such as the stomach, duodenum, ileum, or colon and boosted with intact OVA, OVA-specific antibody production and delayed-type hypersensitivity (DTH) response were significantly enhanced in mice injected into the ileum or colon, compared with orally administered mice. These results suggest that although macromolecular OVA antigens are detected after oral administration of OVA in tolerant-mouse serum, injection of intact OVA cannot contribute to tolerance induction. Therefore, some modification of macromolecular OVA in the gastrointestinal tract and ingestion may be essential for oral tolerance induction.

    DOI： 10.1111/j.1365-2567.2006.02418.x

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  • Induction of immunological tolerance by oral, but not intravenous and intraportal, administration of ovalbumin and the difference between young and old mice Reviewed

    A Wakabayashi, M Utsuyama, T Hosoda, K Sato, H Takahashi, K Hirokawa

    JOURNAL OF NUTRITION HEALTH & AGING   10 ( 3 )   183 - 191   2006.5

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：SERDI EDITION  

    Background: Induction of immunological tolerance is dependent on the route of antigenic administration, the dose of an antigen and the age of animals. Objectives: We investigated the effect of age on the tolerance induction in mice by administration of antigen through different routes and at different doses. Design: Young and old BDF1 mice were orally, intraportally or intravenously administrated with a low or a high dose of ovalbumin (OVA). Then, delayed-type hypersensitivity (DTH) responses and serum anti-OVA antibody levels were assessed after systemic immunization of OVA with alum after appropriate intervals. Results: In the young mice, oral administration of OVA suppressed DTH response and anti-OVA IgG1, IgG2b, IgM and IgE level in a dose-dependent manner. In the old mice, however, the suppression of IgG1 and IgE levels was induced by oral administration of a low dose of OVA, but no suppression by a high dose. On the other hand, intraportal or intravenous injection of OVA did not suppress DTH response and enhanced anti-OVA antibody levels in a dose-dependent manner in both young and old mice. Production of anti-OVA IgG2a antibody after systemic injection of OVA was detected in the mice, which had been treated with intraportal or intravenous injection of OVA, but not detected in the mice, which had been treated with oral administration of OVA. On the contrary, suppression of anti-OVA IgE antibody was observed only in the mice, which had been treated with oral administration of OVA. Conclusion: The oral administration of OVA, neither intravenous nor intraportal, induced immunological tolerance to OVA. An adequate dose of OVA for the tolerance induction and the suppression of antibody production are different between young and old mice. The suppression of IgE antibody was observed only by oral administration of OVA, much obviously in young mice than in the old. The results also indicated that the antigen processing in the liver did not play a major role in the induction of oral tolerance to OVA.

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  • Resistance to viral infection by intraepithelial lymphocytes in HIV-1 P18-I10-specific T-cell receptor transgenic mice. International journal

    Hideki Kuribayashi, Ayako Wakabayashi, Masumi Shimizu, Hiroshi Kaneko, Yoshihiko Norose, Yohko Nakagawa, Jian Wang, Yoshihiro Kumagai, David H Margulies, Hidemi Takahashi

    Biochemical and biophysical research communications   316 ( 2 )   356 - 63   2004.4

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

    For the analysis of mucosal immunity to HIV-1, we have recently established a line of transgenic (Tg) mice expressing the TCRalpha and TCRP genes of the murine CTL clone RT1 specific for P18-I10 (RGPGRAFVTI), an immunodominant gp160 envelope-derived epitope of IIIB isolate, restricted by the H-2D(d) MHC-I molecule. Here we examine those cells bearing specific TCR among the intraepithelial lymphocytes (IELs), with flow cytometric analysis using H-2D(d)/P18-I10 tetramers. We observed three distinct CD3(+), tetramer positive populations among the lELs: extra-thymic CD8alphaalpha(+), alphabetaTCR T-cells; CD8alphaalpha(+), gammadeltaTCR T-cells; and thymus-derived CD8alphabeta(+), alphabetaTCR T-cells. Challenge of these Tg mice with P18-I10 encoded by a vaccinia virus vector, either intrarectally (i.r.) or intraperitoneally (i.p.), revealed that the intraepithelial compartment seems to be a major site for prevention of the spread of viral infection. Such immunity appears due to the thymus-derived, CD8alphabeta(+) antigen-specific CTLs together with CD8alphaalpha(+) gammadelta cells, which regulate virus spread. This model system for studying CTL based immunity at mucosal sites should prove helpful in developing rational approaches for HIV control. (C) 2004 Elsevier Inc. All rights reserved.

    DOI： 10.1016/j.bbrc.2004.02.058

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  • The effects of allopurinol on immune function in normal BALB/c and SCID mice Reviewed

    C Kato, K Sato, A Wakabayashi, Y Eishi

    INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY   22 ( 7 )   547 - 556   2000.7

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

    To clarify the relationship between purine metabolism and immunity, the in vivo immunosuppressive effects of allopurinol (AL), a xanthinoxidase (XO) inhibitor, were studied using normal BALB/c and severe combined immunodeficient (SCID) mice. Following AL administration for 14 weeks (long term), a decreased immune response to ovalbumin (OVA) in the peripheral blood was observed in normal mice, which might not be only due to direct B cell suppression but also due to suppression of helper T cell function. In the SCID mice, there was a markedly late and reduced recovery of surface immunoglobulin (sIg) positive cells, which are markers for mature B lymphocytes, in the peripheral blood after AL administration. The total immunoglobulin G (IgG) titers in the AL treated group were significantly lower than in the control group 6 weeks after stem cell transfer, but increased until there was no difference in the titers between the two groups at week 14. CD4 positive helper T cells and CD8 positive T cells were slow to recover, though these gradually recovered to reach normal levels in the mature stage. These data suggest that the administration of AL may modulate B cell and T cell responses in OVA-immunized antibody formation. Furthermore, this study showed that AL could influence immune functions during the pre-natal and developmental periods and that its effects might differ according to the stages of maturity of the immune cells. (C) 2000 International Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved.

    DOI： 10.1016/S0192-0561(00)00018-7

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  • Vitamin E enhances the immune functions of young but not old mice under restraint stress Reviewed

    A Wakikawa, M Utsuyama, A Wakabayashi, M Kitagawa, K Hirokawa

    EXPERIMENTAL GERONTOLOGY   34 ( 7 )   853 - 862   1999.11

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

    Young and old C57BL/6 male mice were given a diet containing a high dose of vitamin E (VE treatment) and its effect on the immune system was examined before and after the exposure to restraint stress. The VE treatment per se gave rise to a slight increase of splenic T cells in percentage and a significant enhancement of Con A response of spleen cells in young, but not in old mice. The VE treatment also resulted in the enhancement of production of IL-2 and IFN gamma in young, but not in old mice. Restraint stress led to thymic involution in both young and old mice. This thymic involution was not ameliorated by the VE treatment. Percentage of splenic T cells and their mitogenic response decreased just after the stress, but soon rebounded over the control level. The VE treatment further enhanced the recovery after the stress in young mice, but on the contrary suppressed the recovery in old mice. The results in the present study suggested that the VE treatment was effective in the prevention of immunological decline of young mice before and after the exposure to the stress. On the other hand, such a preventive effect was not observed in old mice that were already in the depressed state of immunological functions. (C) 1999 Elsevier Science Inc. All rights reserved.

    DOI： 10.1016/S0531-5565(99)00055-8

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  • Differential age effect of oral administration of an antigen on antibody response: an induction of tolerance in young mice but enhancement of immune response in old mice Reviewed

    A Wakabayashi, M Utsuyama, T Hosoda, K Sato, K Hirokawa

    MECHANISMS OF AGEING AND DEVELOPMENT   109 ( 3 )   191 - 201   1999.9

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI IRELAND LTD  

    Sheep red blood cells (SRBC) were orally administered to young (4 months old) and old (22 months old) mice, and its effect on the antibody production after systemic immunization was compared between young and old mice. The results showed that the dose-dependent suppression of antibody response (oral tolerance) was observed in young mice which had been previously treated with oral administration of SRBC. On the contrary, the enhancement of antibody production was observed in old mice which had been treated in the same way. The enhanced level of IgG antibody in old mice was higher than that of young mice. The critical age determining either suppression or enhancement of antibody response after the oral administration of the antigen was present between 6.5 and 10.5 months of age. When the oral administration of the antigen was performed in young (3 months old) and middle-aged mice (12 months old), the oral tolerance for young and the enhanced antibody response for middle-aged mice were observed even at 6 months after the treatment. The analysis by in vitro antibody response using T and B cells prepared from young and old mice showed that age-related alteration of T and B cells is responsible for the suppression and the enhancement of antibody response after oral administration of SRBC, respectively. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

    DOI： 10.1016/S0047-6374(99)00036-6

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  • Age-related alteration of cytokine production profile by T cell subsets in mice: A flow cytometric study Reviewed

    A Wakikawa, M Utsuyama, A Wakabayashi, M Kitagawa, K Hirokawa

    EXPERIMENTAL GERONTOLOGY   34 ( 2 )   231 - 242   1999.4

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

    Spleen cells from young and old C57BL/6 mice were stimulated with a combination of anti-CD3 and anti-CD28 antibodies, and the profile of cytokine production was examined by two different methods; the concentrations of cytokines as measured by ELISA, and identification of cytokine-positive cells by flow cytometry. The ELISA method revealed that IL-2 production by spleen cells after stimulation was significantly lower in the old mice compared to the young mice, while IFN-gamma production was the reverse. The flow cytometric analysis showed that the percentage of IL-2-positive cells in spleen cells after the stimulation was significantly lower in the older mice than in the young mice, and vice versa for the percentage of IFN-gamma-positive cells. Regarding the T cell subsets, CD4(+) T cells were a major source of IL-2 in both the young and old mice. IL-2-positive cells in both CD4(+) and CD8(+) T cells showed a significant decrease with age. On the contrary, CD8+ T cells were the major source of IFN-gamma. An age-related increase of IFN-gamma-positive cells was observed in both CD4(+) and CD8(+) T cells. CD4(+) T cells were the major source of IL-4, and the percentage of IL-4-positive CD4+ T cells also increased with age, although the level of IL-4 production was modest in C57BL/6 mice compared with IL-2 and IFN-gamma. Such age-related changes of cytokine production are presumed to play an important role in the alteration of immunological capacity with age. (C) 1999 Elsevier Science Inc. All rights reserved.

    DOI： 10.1016/S0531-5565(98)00062-X

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  • Regulation of experimental autoimmune orchitis by the presence or absence of testicular antigens during immunological development in SCID mice reconstituted with fetal liver cells Reviewed

    A Wakabayashi, Y Eishi, K Nakamura

    IMMUNOLOGY   92 ( 1 )   84 - 90   1997.9

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL SCIENCE LTD  

    Severe combined immunodeficient (SCID) mice were immunologically reconstituted by the transfer of fetal liver cells (FLC) of BALB/c mice (SCID-FLC mice). In peripheral blood (PB) of SCID-FLC mice, B and T cells started to appear 2 and 5 weeks, respectively, after the transfer of FLC, and had attained normal levels by 7 weeks. Orchidectomy and transplantation of testis under the kidney capsule were conducted at various stages of immunological maturation, and the induction of experimental autoimmune orchitis (EAO) was performed after immunological maturation in SCID-FLC mice. The experimental system was used to establish that the presence of testicular antigens in the early stage of immunological development influences the induction of EAO; grade of EAO was reduced in the presence of the antigens, and enhanced in their absence. In other words, the existence of self tissue antigens in the early stage of immunological development was essential for proper establishment of tolerance to the self tissue. These findings suggested that the SCID-FLC mouse is a suitable model with which to analyse the interaction between self antigens and cells of the developing immune system, which is otherwise observed only in the fetal or perinatal stage in experimental animals.

    DOI： 10.1046/j.1365-2567.1997.00316.x

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  • Development of the immune system in severe combined immunodeficiency mice reconstituted with transfered fetal liver cells Reviewed

    Ayako Wakabayashi, Yoshinobu Eishi, Kyoichi Nakamura

    Journal of Medical and Dental Sciences   44 ( 1 )   21 - 29   1997

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    Language：English   Publishing type：Research paper (scientific journal)  

    Severe combined immunodeficiency (SCID) mice were immunologically reconstituted by the transfer of fetal liver cells (FLC) from BALB/c (SCID-isoFLC mice) or C57BL/6 mice (SCID-alloFLC mice). The developmental process of the immune system in the peripheral blood (PB) was almost comparable between SCID-isoFLC and SCID-isoFLC mice. Analysis of the lymphoid organs and the PB from SCID-alloFLC mice indicated that slg + B cells appeared and were distributed to the periphery within 2 weeks after the transfer of FLC. It was also suggested that precursor T cells entered the thymus before 4 weeks after the transfer, and were differentiated into mature CD4 + or CD8 + T cells which then migrated to the periphery by 6 weeks. All of mature lymphocytes in the periphery of the SCID-alloFLC mice were shown to express donor-type H-2 antigens. Additionally, in the SCID-isoFLC mice, cell-mediated immunity such as rejection against alloantigens was functioning from 6 weeks, and humoral immune function was suggested by the detection of cells generating antigen-specific antibodies. We discuss that development of the immune system in SCID mice receiving transferred FLC was comparable to that normally seen in the fetal and neonatal stages.

    DOI： 10.11480/jmds.440103

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Presentations

  • An aluminum-containing food additive causes cleavage of IL-18, IL-33 and gasdermin D in intestinal epithelial cells under antibiotic treatment

    Ayako Wakabayashi, Atsuko Owaki, Ken Iwatsuki, Etsuko Toda, Yasuhiro Nishiyama, Shoji Matsune, Rimpei Morita

    The 52nd Annual Meeting of The Japanese Society for Immunology  2024.1 

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    Event date： 2024.1

    Language：English   Presentation type：Oral presentation (general)  

    Country：Japan  

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  • An aluminum-containing food additive causes cleavage of IL-33 and gasdermin D in intestinal epithelial cells under antibiotic-treatment International conference

    Ayako Wakabayashi, Atsuko Owaki, Ken Iwatsuki, Keisuke Tanaka, Soichiro Kumamoto, Yuuichi Koshiishi, Yasutaka Osada, Yasuhiro Nishiyama, Shoji Matsune, Rimpei Morita

    The World Allergy Congress (WAC) 2023  2023.12 

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    Event date： 2023.12

    Language：English   Presentation type：Poster presentation  

    Venue：Bangkok   Country：Thailand  

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  • An aluminum-containing food additive causes pyroptosis and IL-18 production in intestinal epithelial cells under antibiotic treatment

    Ayako Wakabayashi, Atsuko Owaki, Ken Iwatsuki, Keisuke Tanaka, Soichiro Kumamoto, Yuuichi Koshiishi, Yasutaka Osada, Yasuhiro Nishiyama, Shoji Matsune, Rimpei Morita

    2023.10 

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    Event date： 2023.10

    Language：English   Presentation type：Oral presentation (general)  

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  • 抗生剤が促進する食品添加物ミョウバンによる腸管上皮の炎症性細胞死の解析

    若林あや子, 大脇敦子, 長田康孝, 森田林平

    文部科学省科学技術人材育成費補助事業「ダイバーシティ研究環境実現イニシアティブ(牽引型)」 2022年度共同研究・研究支援員配置 研究成果発表会  2023.9 

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    Event date： 2023.9

    Language：Japanese   Presentation type：Oral presentation (invited, special)  

    Venue：Web開催  

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  • アルミニウム含有食品添加物は腸上皮細胞において細胞死に関わるカスパーゼを活性化する

    若林あや子, 西山康裕, 松根彰志, 森田林平

    第 91 回日本医科大学医学会学術集会  2023.9 

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    Event date： 2023.9

    Language：Japanese   Presentation type：Poster presentation  

    Venue：東京, Web  

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  • Antibiotics promote epithelial cell death and eosinophilic infiltration in the gut caused by an aluminum-containing food additive

    Ayako Wakabayashi, Atsuko Owaki, Ken Iwatsuki, Yasuhiro Nishiyama, Shoji Matsune, Rimpei Morita

    2022.12 

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    Event date： 2022.12

    Language：English   Presentation type：Poster presentation  

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  • Antibiotics-induced dysbiosis promotes epithelial cell death and eosinophilic infiltration in the gut caused by aluminum-containing food additives

    Ayako Wakabayashi, Atsuko Owaki, Ken Iwatsuki, Keisuke Tanaka, Soichiro Kumamoto, Yasutaka Osada, Yasuhiro Nishiyama, Shoji Matsune, Rimpei Morita

    第71回日本アレルギー学会学術集会  2022.10 

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    Event date： 2022.10

    Language：English   Presentation type：Oral presentation (general)  

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  • アレルギーの食品栄養学

    若林あや子

    2022年度第17期アレルギー大学 in 千葉 ベーシックプログラム  2022.7 

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    Event date： 2022.7

    Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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  • An aluminum-containing food additive upregulates gene expression involved in inflammatory cell death in intestinal epithelial cells

    2021.12 

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    Event date： 2021.12

    Presentation type：Poster presentation  

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  • Increased inflammatory cell death in intestinal epithelial cells by oral administration of aluminum salt as a food additive

    Ayako Wakabayashi, Atsuko Owaki, Ken Iwatsuki, Keisuke Tanaka, Yasutaka Osada, Yasuhiro Nishiyama, Shoji Matsune, Rimpei Morita

    第70回日本アレルギー学会学術大会  2021.10 

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    Event date： 2021.10

    Language：English   Presentation type：Poster presentation  

    Country：Japan  

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  • アルミニウム含有食品添加物で誘導されるアレルギーと腸管上皮細胞死の解析

    若林あや子, 大脇敦子, 岩槻健, 田中啓介, 長田康孝, 西山康裕, 松根彰志, 森田林平

    第75回 日本栄養・食糧学会大会  2021.7 

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    Event date： 2021.7

    Language：Japanese   Presentation type：Poster presentation  

    Venue：Web開催   Country：Japan  

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  • 食物アレルギーと腸管免疫 Invited

    若林あや子

    令和３年度日本女子大学食物学科縦の会講演会  2021.6 

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    Event date： 2021.6

    Language：Japanese   Presentation type：Oral presentation (invited, special)  

    Venue：Web開催  

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  • Antigen sensitization and intestinal infiltration of eosinophils by oral administration of aluminum salt as a food additive International conference

    Ayako Wakabayashi, Atsuko Owaki, Masumi Shimizu, Ken Iwatsuki, Rimpei Morita

    JSA/WAO joint Congress 2020・第69回日本アレルギー学会学術大会  2020.9 

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    Event date： 2020.9 - 2020.10

    Language：English   Presentation type：Poster presentation  

    Venue：Web   Country：Japan  

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  • Damage and enhanced cytoplasmic IL-33-expression in EpCAM+ intestinal epithelial cells and antigen sensitization by oral aluminum salt

    Ayako Wakabayashi, Shuji Toriumi, Eri Koike, Yasuhiro Nishiyama, Rimpei Morita, Hidemi Takahashi

    第48回日本免疫学会学術集会  2019.12 

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    Event date： 2019.12

    Language：English   Presentation type：Poster presentation  

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  • HMGB1 released from damaged intestinal epithelia activates mucosal dendritic cells and induces intestinal cytotoxic T lymphocytes and IgA International conference

    Ayako Wakabayashi, Masumi Shimizu, Eiji Shinya, Rimpei Morita, Hidemi Takahashi

    9th International DAMPs and Alarmins Symposium  2019.11 

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    Event date： 2019.11

    Language：English   Presentation type：Poster presentation  

    Venue：Okayama   Country：Japan  

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  • アレルギーの食品栄養学

    アレルギーの食品栄養学

    アレルギー大学（千葉）ベーシックプログラム  2019.7 

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    Event date： 2019.7

    Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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  • Induction of damage of EpCAM+ intestinal epithelial cells and antigen sensitization by aluminum salt as a food additive

    Ayako Wakabayashi, Shuji Toriumi, Masumi Shimizu, Yasuhiro Nishiyama, Hidemi Takahashi

    第68回日本アレルギー学会学術大会  2019.6 

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    Event date： 2019.6

    Language：English   Presentation type：Oral presentation (general)  

    Venue：Tokyo   Country：Japan  

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  • HMGB1 released from damaged intestinal epithelia contributes to activation of mucosal DCs and induction of intestinal CTLs and IgA International conference

    Ayako Wakabayashi, Masumi Shimizu, Eiji Shinya, Hidemi Takahashi

    23rd Edition of International Conference on Immunology and Infectious Diseases  2019.4 

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    Event date： 2019.4

    Language：English   Presentation type：Oral presentation (general)  

    Venue：London   Country：United Kingdom  

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  • 経口免疫法による抗腫瘍ワクチンの開発

    若林あや子, 高橋秀実

    第1回中央大学・日本医科大学学術合同ワークショップ  2008.5 

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    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

    Venue：Tokyo  

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  • Induction of ovalbumin-specific cytotoxic cells in both intestinal intraepitherial lymphocytes and spleen cells by oral administration of ovalbumin plus cholera toxin International conference

    Ayako Wakabayashi, Yohko Nakagawa, Yasuhiro Nishiyama, Yoshiyuki Watanabe, Rie Goto, Yoshihiro Kumagai, Hidemi Takahashi

    12th International Congress of Immunology and 4th Annual Conference of FOCIS  2004.7 

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  • OVA経口免疫による小腸上皮間リンパ球におけるOVA特異的CTLの誘導とOVA発現腫瘍に対する成長抑制効果

    若林あや子, 守屋慶一, 中川洋子, 野呂瀬嘉彦, 熊谷善博, 高橋秀実

    第34回日本免疫学会  2004.12 

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    Language：Japanese  

    Venue：Sapporo  

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  • Importance of gastrointestinal ingestion and macromolecular antigens in the vein for oral tolerance induction

    Ayako Wakabayashi, Yoshihiro Kumagai, Eiji Watari, Masumi Shimizu, Keiichi Moriya, Masanori Utsuyama, Katsuiku Hirokawa, Hidemi Takahashi

    第36回日本免疫学会学術集会  2006.12 

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    Language：English  

    Venue：Osaka  

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  • OVAの門脈投与により免疫寛容は誘導されない

    若林あや子, 宇津山正典, 熊谷善博, 高橋秀実, 広川勝昱

    第29回日本免疫学会総会  1999.12 

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    Language：Japanese  

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  • 免疫寛容における抗原の腸管通過の必要性：OVAの門脈投与により抗原特異的免疫反応は亢進する

    や子, 宇津山正典, 熊谷善博, 高橋秀実, 広川勝昱

    第54回日本栄養・食糧学会大会  2000.5 

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    Venue：Matsuyama  

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  • OVAに対する免疫寛容誘導における胃液処理の関与

    若林あや子, 中川洋子, 清水真澄, 熊谷善博, 高橋秀実

    第30回日本免疫学会総会  2000.11 

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    Language：Japanese  

    Venue：Sendai  

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  • Analysis of the mechanisms of oral tolerance mediated in OVA-immunized mice: detection of antigenic OVA fragments in the sera International conference

    Ayako Wakabayashi, Eiji Watari, Megumi Takahashi, Yoshihiro Kumagai, Katsuiku Hirokawa, Hidemi Takahashi

    11th International Congress of Immunology  2001.7 

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    Language：English   Presentation type：Poster presentation  

    Venue：Stockholm, Sweden  

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  • Differential effect of oral administration of an antigen on antibody response by host age International conference

    hi A, Utsuyama M, Hosoda T, Sato K, Hirokawa K

    6th Asia-Oceania Regional Congress of Gerontology  1999.6 

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  • 経口免疫の加齢変化（3）

    若林あや子, 細田智子, 宇津山正典, 佐藤和人, 広川勝昱

    第22回日本基礎老化学会大会  1999.6 

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    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 漢方補剤による老化マウスの免疫機能の回復効果について

    宇津山正典, 白石純一, 若林あや子, 広川勝昱

    第22回日本基礎老化学会大会  1999.6 

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    Language：Japanese   Presentation type：Oral presentation (general)  

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  • OVAによる経口免疫寛容は若齢マウスでは大量、老齢マウスでは少量の経口投与により誘導される

    若林あや子, 細田智子, 宇津山正典, 佐藤和人, 広川勝昱

    第53回日本栄養・食糧学会大会  1999.5 

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    Language：Japanese  

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  • 経口トレランスは若齢マウスでは誘導されるが老齢マウスでは誘導されない

    細田智子, 若林あや子, 宇津山正典, 佐藤和人, 広川勝昱

    第53回日本栄養・食糧学会大会  1999.5 

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    Language：Japanese  

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  • β-lactoglobulin(β-LG)への免疫応答の変化ならびに経口トレランス(OT)の誘導における感作時期の影響.

    加藤千晶, 野田朋美, 三戸夏子, 高橋恵子, 平沢玲子, 細田智子, 若林あや子, 佐藤和人

    第53回日本栄養・食糧学会大会  1999.5 

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    Language：Japanese  

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  • Induction of tolerance in young but enhancement of immune response in old mice by oral administration of sheep red blood cells (SRBC) International conference

    Wakabayashi A, Utsuyama M, Hosoda T, Sato K, Hirokawa K

    10th International Congress of Mucosal Immunology  1999.6 

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  • リンパ球の加齢変化により経口免疫寛容が誘導されなくなる

    若林あや子, 細田智子, 宇津山正典, 佐藤和人, 広川勝昱

    第88回日本病理学会総会  1999.4 

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    Language：Japanese  

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  • High mobility group box protein 1 released from damaged intestinal epithelial cells triggers antigen sensitization International conference

    Wakabayashi A, Shimizu M, Shinya E, Takahashi H

    The Joint Congress of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology & the Asia Pacific Association of Pediatric Allergy, Respirology and Immunology  2018.10  The Asia Pacific Association of Allergy, Asthma and Clinical Immunology, the Asia Pacific Association of Pediatric Allergy Respirology& Immunology and the Allergy, Asthma and Immunology Association of Thailand

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    Language：English   Presentation type：Poster presentation  

    Venue：Bangkok, Thailand  

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  • HMGB1 released from intestinal epithelia damaged by cholera toxin contributes to activation of mucosal DCs and induction of intestinal CTLs and IgA

    Ayako Wakabayashi, Masumi Shimizu, Michiyuki Yonekawa, Eiji Shinya, Hidemi Takahashi

    第47回日本免疫学会学術集会  2018.12  日本免疫学会

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    Language：English   Presentation type：Poster presentation  

    Venue：Fukuoka, Japan  

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  • Food and nutrition for allergies

    Wakabayashi A

    アレルギー大学（千葉）ベーシックプログラム  2018.7  特定非営利活動法人 千葉アレルギーネットワーク

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    Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

    Venue：Chiba, Japan  

    File： 2018年ベーシックプログラム裏面.pdf

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  • HMGB1 released from intestinal epithelia damaged by cholera toxin activates mucosal DCs and induces cytotoxic T lymphocytes and IgA

    Wakabayashi A, Shimizu M, Shinya E, Takahashi H

    The 27th Annual Meeting of The Japanese Society for Cell Death Research  2018.7  The Japanese Society for Cell Death Research

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    Language：Japanese   Presentation type：Poster presentation  

    Venue：Kyoto, Japan  

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  • HMGB1 released from intestinal epithelia damaged by cholera toxin adjuvant contributes to activation of mucosal DCs and induction of intestinal CTLs and IgA International conference

    Wakabayashi A, Shimizu M, Shinya E, Takahashi H

    5th European Congress of Immunology  2018.9  The European Federation of Immunological Societies

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    Language：English   Presentation type：Poster presentation  

    Venue：Amsterdam, Netherlands  

    File： cOASIS, The Online Abstract Submission System.pdf

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  • Glycyrrhizin inhibits high-mobility group box 1 protein released from damaged intestinal epithelia and antigen sensitization International conference

    Wakabayashi A, Shimizu M, Shinya E, Takahashi H

    11th International Symposium on Immunonutrition  2018.9  International Society for Immunonutrition

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    Language：English   Presentation type：Oral presentation (general)  

    Venue：London, UK  

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  • 樹状細胞亜群の選択的活性化によるアレルギー制御の可能性

    あや子, 根岸靖幸, 廣井隆親, 大久保公裕, 高橋秀実

    第66回日本アレルギー学会学術大会  2017.6 

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    Language：Japanese  

    Venue：Tokyo  

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  • アレルギーの食品栄養学

    若林 あや子

    アレルギー大学（千葉）ベーシックプログラム  2017.7 

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    Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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  • Enhancement of epithelial cell death, cytoplasmic HMGB1 expression in IECs, and increase of HMGB1 release by oral CT-stimulation

    Wakabayashi Ayako, Shimizu Masumi, Yonekawa Michiyuki, Ishii Kazuhito, Kumagai Yoshihiro, Takahashi Hidemi

    第46回日本免疫学会学術集会  2017.12 

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    Language：English   Presentation type：Oral presentation (general)  

    Venue：Sendai  

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  • Epithelial cell damage and high mobility group box protein 1 released from the damaged EpCAM+CD45- intestinal epithelial cells trigger intestinal DC activation and antigen sensitization

    Wakabayashi A, Shimizu M, Yonekawa M, Ishii K, Kumagai Y, Takahashi H

    The 67th Annual Meeting of Japanese Society of Allergology  2018.6  Japanese Society of Allergology

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    Language：English   Presentation type：Oral presentation (general)  

    Venue：Chiba, Japan  

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  • Intestinal DEC-205＋ DCs activated by HMGB-1 released through cholera toxin-stimulation contribute to cross-priming of mucosal CTLs

    WAKABAYASHI Ayako, YONEKAWA Michiyuki, TAKESHITA Hikaru, AZUMA Hideko, KUMAGAI Yoshihiro, TAKAHASHI Hidemi

    第45回日本免疫学会学術集会  2016.12 

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    Language：English   Presentation type：Oral presentation (general)  

    Venue：Okinawa  

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  • 食品学の基礎

    Wakabayashi Ayako

    第12期アレルギー大学（千葉）  2017.6 

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    Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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  • Predominant distribution of DCIR2+ dendritic cells in the intestinal tissues and their activation by with high mobility group box protein 1 released through by cholera toxin

    Wakabayashi Ayako, Yonekawa Michiyuki, Ishii Kazuhito, Takahashi Hidemi

    第66回日本アレルギー学会学術大会  2017.6 

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    Language：English   Presentation type：Oral presentation (general)  

    Venue：Tokyo  

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  • アレルギーの食品栄養学

    Wakabayashi Ayako

    アレルギー大学（千葉）ベーシックプログラム  2016.7 

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    Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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  • Airway allergy can be controlled through dendritic cell subset manipulation in a mouse model International conference

    Hidemi Takahashi, Ryosuke Murakami, Yohko Nakagawa, Masumi Shimizu, Ayako Wakabayashi, Yasuyuki Negishi, Takachika Hiroi, Eiji Shinya, Kimihiro Ohkubo

    16TH International congress of immunology  2016.8 

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    Language：English   Presentation type：Symposium, workshop panel (public)  

    Venue：Melbourne, Australia  

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  • HMGB-1 contributes to the enhancement of co-stimulatory molecule-expression and cross-presentation by mucosal DCs through oral administration of cholera toxin International conference

    Ayako WAKABAYASHI, Michiyuki YONEKAWA, Kazuhito ISHII, Kasumi KUROKI, Eiji SHINYA, Hidemi TAKAHASHI

    16TH International congress of immunology  2016.8 

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    Language：English   Presentation type：Symposium, workshop panel (public)  

    Venue：Melbourne, Australia  

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  • Airway allergy induced by histamine released from IgE–sensitized mast cells can be controlled through dendritic cell subset manipulation in a mouse mode

    Hidemi Takahashi, Ryosuke Murakami, Masumi Shimizu, Ayako Wakabayashi, Hikaru Takeshita, Eri Koike, Yasuyuki Negishi, Sadayuki Ohkura, Kimihiro Ohkubo

    第45回日本免疫学会学術集会  2016.12 

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    Language：English  

    Venue：Okinawa  

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  • 食品学の基礎

    Wakabayashi Ayako

    第11期アレルギー大学（千葉）  2016.6 

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    Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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  • アレルギー性鼻炎マウスモデルにおけるDEC-205陽性樹状細胞亜群選択的活性化による抗アレルギー効果の検討

    村上亮介, 中川洋子, 清水真澄, 若林あや子, 根岸靖幸, 廣井隆親, 大久保公裕, 高橋秀実

    第65回日本アレルギー学会学術大会  2016.6 

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    Language：Japanese  

    Venue：Tokyo  

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  • High mobility group box protein-1 released from damaged intestinal tissues contributes to the activation of mucosal dendritic cells and the sensitization of antigen-specific T cells

    Wakabayashi Ayako, Yonekawa Michiyuki, Ishii Kazuhito, Murakami Ryosuke, Takahashi Hidemi

    第65回日本アレルギー学会学術大会  2016.6 

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    Language：English   Presentation type：Oral presentation (general)  

    Venue：Tokyo  

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  • Enhancement of costimulatory molecule-expression on mucosal DCs by treatment with cholera toxin in vitro

    Wakabayashi A, Otsuka Y, Ishi K, Takahashi H

    第43回日本免疫学会学術集会  2014.12 

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    Language：English  

    Venue：Kyoto  

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  • 食品学の基礎

    Wakabayashi Ayako

    第10期アレルギー大学（千葉）  2015.6 

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    Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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  • アレルギーの食品栄養学

    Wakabayashi Ayako

    アレルギー大学（千葉）ベーシックプログラム  2015.7 

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    Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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  • HMGB-1 contributes to the enhancement of co-stimulatory molecule-expression on mucosal DCs by oral administration of cholera toxin

    Wakabayashi A, Yonekawa M, Ishii K, Murakami R, Date T, Takahashi H

    第44回日本免疫学会学術集会  2015.11 

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    Language：English  

    Venue：Sapporo  

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  • Enhancement of OVA-specific IgG and IgE production and expression of costimulatory molecules on dendritic cells in the mesenteric lymphonodes by oral administration of OVA plus potassium alum

    Wakabayashi A, Nakagawa Y, Shimizu, M, Murakami R, Date T, Takahashi H

    第42回日本免疫学会学術集会  2013.12 

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    Language：English  

    Venue：Makuhari  

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  • 食品学の基礎 Invited

    Wakabayashi Ayako

    第9期アレルギー大学（千葉）  2014.6 

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    Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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  • アレルギーの食品栄養学 Invited

    Wakabayashi Ayako

    アレルギー大学（千葉）ベーシックプログラム  2014.8 

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    Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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  • アレルギーの食品栄養学 Invited

    Wakabayashi Ayako

    アレルギー大学（沖縄）ベーシックプログラム  2014.10 

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    Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

    Venue：沖縄  

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  • アレルギー性鼻炎マウスモデルにおける樹状細胞特異的33D1抗体投与の影響

    村上 亮介, 中川 洋子, 清水 真澄, 根岸 靖幸, 若林 あや子, 大久保 公裕, 高橋 秀実

    第63回日本アレルギー学会秋期学術大会  2013.11 

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    Venue：Tokyo  

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  • みょうばんとOVAの経口投与による消化管樹状細胞の活性化および特異的IgG・IgE産生の亢進

    若林 あや子, 中川 洋子, 清水 真澄, 野呂瀬 嘉彦, 高橋 秀実

    第63回日本アレルギー学会秋期学術大会  2013.11 

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    Venue：Tokyo  

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  • Effect of depletion of 33D+ dendritic cells on allergic airway sensitization in mouse model International conference

    Murakami R, Nakagawa Y, Wakabayashi A, Kumagai Y, Ohkubo K, Takahashi H

    The 15th International Congress of Immunology  2013.8 

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    Language：English  

    Venue：Milan  

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  • アレルギー食の知識：食物アレルギーについて

    Wakabayashi Ayako

    アレルギー食事故防止対策研修会  2013.2 

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    Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

    Venue：Tokyo  

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  • Depletion of 33D1+DC subset will induce fetal loss in pregnant mice though IL-12 secretion International conference

    Negishi, Y, Wakabayashi, A, Shimizu, Negishi Y, Wakabayashi A, Shimizu M, Ichikawa T, Takeshita T, Takahashi H

    The 33th American Society of Reproductive Immunology  2013.5 

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    Language：English  

    Venue：Hamburg  

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  • 栄養と食品を学ぶために Invited

    Wakabayashi Ayako

    第8期アレルギー大学（千葉）  2013.6 

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  • Fetal loss induced by depletion of innate 33D1+DC subset in mice International conference

    Negishi Y, Wakabayashi A, Shimizu M, Matsuhashi T, Ichikawa T, Takeshita T, Takahashi

    The 15th International Congress of Immunology  2013.8 

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    Language：English  

    Venue：Milan  

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  • 粘膜免疫賦活による抗腫瘍免疫の誘導 Invited

    Wakabayashi Ayako

    第18回千駄木感染免疫アレルギー研究会  2008.3 

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    Venue：Tokyo  

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  • 抗生剤が促進する食品添加物ミョウバンによる腸管上皮の炎症性細胞死の解析

    若林あや子, 大脇敦子, 長田康孝, 森田林平

    文部科学省科学技術人材育成費補助事業「ダイバーシティ研究環境実現イニシアティブ(牽引型)」2021年度共同研究・研究支援員配置 研究成果発表会  2022.6 

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  • イヌの肝細胞癌のオルガノイドバンクの構築および新規治療法の開発

    町田雪乃, 道下正貴, 若林あや子

    文部科学省科学技術人材育成費補助事業「ダイバーシティ研究環境実現イニシアティブ(牽引型)」2021年度共同研究・研究支援員配置 研究成果発表会  2022.6 

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  • アレルギーの食品栄養学

    若林あや子

    アレルギー大学（千葉）ベーシックプログラム  2020.7  特定非営利活動法人 千葉アレルギーネットワーク

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    Language：Japanese  

    Venue：オンライン  

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  • アレルギーの食品栄養学

    若林あや子

    アレルギー大学（千葉）ベーシックプログラム  2021.7  特定非営利活動法人 千葉アレルギーネットワーク

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    Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

    Venue：Web開催   Country：Japan  

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  • エイズウイルス外被糖蛋白特異的CD8陽性細胞障害性T細胞の遊離エピトープペプチドによるin vivoでのアポトーシス誘導とその制御

    中川洋子, 清水真澄, 野呂瀬嘉彦, 若林あや子, 高橋めぐみ, 高橋秀実

    第25回日本エイズ学会学術集会  2011.11 

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    Venue：Tokyo  

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  • 栄養と食品を学ぶために Invited

    Wakabayashi Ayako

    第７期アレルギー大学（千葉）  2012.7 

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  • CD8+CD103+ dendritic cells in the mesenteric lymph-nodes cross-present exogenous antigens captured through DEC-205 receptor when they are orally administered with cholera toxin

    Ayako Wakabayashi, Yohko Nakagawa, Masumi Shimizu, Hidemi Takahashi

    第41回日本免疫学会学術集会  2012.12 

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    Venue：Kobe  

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  • Maternal immune balance maintained by innate DC subsets appears to regulate pregnancy in mice

    Negishi Yasuyuki, Wakabayashi Ayako, Shimizu Masumi, Ichikawa Tomoko, Takeshita Toshiyuki, Takahashi Hidemi

    第41回日本免疫学会学術集会  2012.12 

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    Venue：Kobe  

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  • Enhancement of co-stimulatory molecule-expression and cross-presentation of antigens in mucosal DCs after oral administration of antigenic molecules plus cholera toxin

    Ayako Wakabayashi, Yohko Nakagawa, Masumi Shimizu, Hidemi Takahashi

    第４０回日本免疫学会学術集会  2011.11 

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    Language：English  

    Venue：Makuhari  

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  • アレルギーの食品・栄養学・初級編 Invited

    Wakabayashi Ayako

    第５期アレルギー大学（千葉）  2010.10 

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  • 栄養と食品を学ぶために Invited

    Wakabayashi Ayako

    第６期アレルギー大学（千葉）  2011.7 

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  • マウスにおける33D1+およびDEC-205+樹状細胞のサイトカイン産生と腫瘍増殖抑制に対する効果

    守屋慶一, 若林あや子, 清水真澄, 渡辺恵理, 田村秀人, 壇和夫, 高橋秀実

    第70回日本血液学会総会  2008.10 

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    Venue：Kyoto  

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  • Enhancement of expression DEC-205 and co-stimulatory molecules in intraepitherial DCs after oral administration of an antigen and its involvement in mucosal CTL induction

    Wakabayashi A, Moriya K, Harimoto K, Watari E, Takahashi H

    第38回日本免疫学会総会  2008.12 

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    Venue：Kyoto  

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  • Induction of acquired tumor-specific immunity against already established tumors by selective stimulation of innate DEC-205+ dendritic cells with very low-dose of anti-cancer drugs in vivo

    Wakabayashi A, Moriya K, Harimoto H, Tomita Y, Shimizu M, Takahashi H

    第39回免疫学会学術集会  2009.12 

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  • Induction of tumor-specific acquired immunity against already established tumors by selective stimulation of innate DEC-205+ dendritic cells International conference

    Ayako Wakabayashi, Keiichi Moriya, Masumi Shimizu, Hidemi Takahashi

    14th International Congress of Immunology  2010.8 

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    Venue：Kobe, Japan  

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  • Effect of gastrointestinal ingestion of orally administered macromolecular antigens on the induction of oral tolerance International conference

    Wakabayashi A, Kumagai Y, Watari E, Shimizu M, Utsuyama M, Hirokawa K, Takahashi H

    13th International Congress of Mucosal Immunology  2007.7 

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    Venue：Tokyo, Japan  

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  • Effects of 33D1+ or DEC-205+ dendritic cell depletion on cytokine secretion and tumor growing in mice

    Moriya K, Wakabayashi A, Shimizu M, Watanabe E, Takaku S, Dan K, Takahashi H

    第37回日本免疫学会学術集会  2007.11 

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Awards

  • 公益財団法人日本食品化学研究振興財団助成金

    2019.4   ミョウバンによる腸管上皮損傷に伴う炎症・アレルギー誘導性損傷関連分子の放出の解析と免疫学的安全性評価の検討

    若林あや子

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  • The Award in Maruyama's memory

    2008   Nippon Medical School  

    Ayako Wakabayashi

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Research Projects

  • ヒト好酸球性鼻副鼻腔炎病態でのtype２炎症と腸内カンジダ増殖の関連についての研究

    Grant number：24K12659  2024.4 - 2028.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    松根彰志、森田林平、許田典男、若林あや子、大橋隆治、大久保公裕

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    Authorship：Coinvestigator(s) 

    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

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  • カスパーゼ-1およびカスパーゼ-11阻害剤による腸上皮細胞死の抑制と腸管2型炎症の改善の検討

    2024.4 - 2025.3

    文部科学省科学技術人材育成費補助事業 ダイバーシティ研究環境実現イニシアティブ(牽引型) 共同研究 

    若林あや子, 遠田悦子, 町田雪乃

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  • 共役リノール酸を高めた乳あるいは肉の生産およびその摂取による肥満の改善

    2024.4 - 2025.3

    文部科学省科学技術人材育成費補助事業 ダイバーシティ研究環境実現イニシアティブ（女性リーダー育成型）飛躍的共同研究費助成 

    前田友香, 植木美希, 桑原考史, 江草愛, 若林あや子

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  • A food additive containing aluminum causes cleavage of interleukin-33 and gasdermin D in intestinal epithelial cells under antibiotic treatment

    2023.12

    Ayako Wakabayashi

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  • Analysis of intestinal bacterial invasion into intestinal epithelial cells and inflammation induction by an aluminum-containing food additive alum

    Grant number：22K11763  2022.4 - 2026.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

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    Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）

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  • 食品添加物ミョウバン刺激後に腸上皮細胞に侵入して炎症性細胞死を誘導する腸内マイクロバイオームへ抗生剤が与える影響の16S rRNAメタゲノム解析

    2021.10 - 2022.3

    2021年度（後期）東京農業大学生物資源ゲノム解析センター 生物資源ゲノム解析拠点 共同研究 

    若林あや子, 森田林平, 岩槻健, 隈本宗一郎

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  • イヌの肝細胞癌のオルガノイドバンクの構築および新規治療法の開発

    2021.4 - 2025.3

    文部科学省科学技術人材育成費補助事業 ダイバーシティ研究環境実現イニシアティブ（牽引型）共同研究 

    町田雪乃, 道下正貴, 若林あや子

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    Authorship：Coinvestigator(s) 

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  • 抗生剤が促進する食品添加物ミョウバンによる腸管上皮の炎症性細胞死の解析

    2021.4 - 2023.3

    2021-2022年度 文部科学省科学技術人材育成費補助事業 ダイバーシティ研究環境実現イニシアティブ（牽引型）共同研究 

    若林あや子, 森田林平, 長田康孝, 大脇敦子

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    Authorship：Principal investigator 

    Grant amount：\1000000 （ Direct Cost: \1000000 ）

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  • 腸内細菌叢および腸管上皮細胞からのDAMPs制御による脳虚血病巣進展への影響

    2020.4 - 2022.3

    新潟大学脳研究所 脳神経病理資源活用の疾患病態共同研究拠点 共同研究 

    西山康裕, 五十嵐博中, 若林あや子

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    Authorship：Coinvestigator(s) 

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  • 食品添加物ミョウバンによるマウス腸上皮細胞インフラマソーム活性化のトランスクリプトーム解析

    2020.4 - 2020.9

    2020年度（前期）東京農業大学生物資源ゲノム解析センター 生物資源ゲノム解析拠点 共同研究 

    若林あや子, 岩槻健, 田中啓介, 森田林平

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  • Release of damage-associated molecular patterns from intestinal epithelia by aluminum salt and involvement in the development of food allergy

    Grant number：19K11703  2019.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

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    Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）

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  • 好酸球性副鼻腔炎病態への腸内フローラ、カンジダ増殖関与についての予備的研究

    Grant number：19K09917  2019.4 - 2023.3

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    松根 彰志, 大橋 隆治, 吾妻 安良太, 大久保 公裕, 若林 あや子, 若山 望

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    Grant amount：\4290000 （ Direct Cost: \3300000 、 Indirect Cost：\990000 ）

    平成27年以来難病指定の対象となっている好酸球性副鼻腔炎(ERS)の病態は未詳、不明の点が多い。アスピリン喘息を含む喘息を合併することが多い本疾患は、治療に関して手術後のステロイド経口投与、新規の抗体治療に頼ることが多く対策が求められている。そこで、従来の本疾患の病態解明へのアプローチとは異なった「腸内フローラにおける真菌、特にカンジダの増加」を想定し、通常の臨床で得られる患者背景因子、採血や手術標本で得られるバイオマーカー等を詳細に検討しその可能性を本研究では明らかにすることを目的とする。その後に、症例の糞便を標本としたDNAシークエンス等による腸内フローラにおけるカンジダの増減、多寡の検討等に繋げる。その結果は、腸内フローラをターゲットとした好酸球性副鼻腔炎の予防、診断キットの開発などの新規の診断方法、治療法の開発に寄与する。
    日本医科大学倫理員会の承認が得られ、本研究を開始する環境が整った。これまでの病態論とは全く異なった切り口で、新しい病態論の検討を開始する。これまでの、好酸球性副鼻腔炎やLocal Allergic Rhinitisの研究実績が無事論文に掲載され、当研究室における鼻副鼻腔粘膜での総IgE,特異的IgEの産生に関する解析能力に問題が無いことが実証された。こうした当教室の研究能力を基本に本研究も推進することが可能である。

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  • ミョウバンによる腸管上皮損傷に伴う炎症・アレルギー誘導性損傷関連分子の放出の解析と免疫学的安全性評価の検討

    2019.4 - 2022.3

    公益財団法人日本食品化学研究振興財団助成金 

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    Authorship：Principal investigator 

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  • Gut microbiotaの制御が脳虚血病巣進展および神経機能に及ぼす影響

    Grant number：17K01477  2017.4 - 2023.3

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    西山 康裕, 五十嵐 博中, 若林 あや子

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    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

    Liらの報告(Immunity.2015;43:527)に基づき C57BL/6Jマウスに対して抗生物質の混合含有水投与を行い１４日間投与を続けた。本学動物実験規程に基づき、総頸動脈からシリコンコートした塞栓糸を挿入して中大脳動脈内を閉塞、 ６０分後に塞栓糸を抜去し、急性脳梗塞モデルとした(中大脳動脈閉塞術(MCAO モデル))。脳梗塞モデルで抗生物質投与の有無により、腸管免疫担当細胞を解析した。脳梗塞については、同様に２４時間後、７２時間後に解析する予定であった。しかしながら、６０分モデルではモデルが安定せず、マウス死亡率が高いため、実験としての再現性が問題と考え、４５分虚血にて行った。これにより生存率が安定し、実験としての継続可能と判断に至った。TTC染色を行い、TTC染色で染色されない梗塞巣を両群間で比較した。このとき、皮質領域、基底核領域については各々測定した。また、同時に脳浮腫率も測定した。さらに、脳虚血前および２４時間後、７２時間後に神経学的スコアを計測し、両群間で比較した。なお、脳浮腫率は脳浮腫率（％）＝〔虚血半球－対側半球〕×１００／対側半球で計算した。結果として、１）平均の飲水量は両群ともに一日6mLで有意差を認めなかった。２）抗生物質投与１４日間でマウスの体調に変化は認めず、死亡例はなかった。３）虚血後２４時間の梗塞サイズにおいて、健常側比にて皮質、基底核および全脳いずれにおいてもvehicle群と抗生物質投与群に統計学的有意差を認めず、脳浮腫率においても、両群間で有意差を認めなかった。４）虚血後72時間の梗塞サイズにおいて、健常側比にて皮質および全脳においてvehicle群と抗生物質投与群に統計学的有意差を認めた。脳浮腫率においては両群間で有意差を認めなかった。血清中および腸管組織に対して各種サイトカイン、HMGB1などを測定していく予定である。

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  • Damage-associated molecular pattern released from intestinal epithelia damaged by bacterial exotoxin induces food allergy

    Grant number：15K00889  2015.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Wakabayashi Ayako

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    Grant amount：\3900000 （ Direct Cost: \3000000 、 Indirect Cost：\900000 ）

    Cholera toxin (CT) is a mucosal adjuvant and oral administration of ovalbumin (OVA) plus CT induces OVA-specific T cell responses and antibody production in mice.
    We showed that oral CT enhances expression of CD80 and CD86 and antigen presentation to T cells of intestinal dendritic cells (DCs). We found that oral CT enhances cell death and cytoplasmic expression of high-mobility group box 1 protein (HMGB1) in intestinal epithelial cells (IECs), and fecal HMGB1 levels. HMGB1 dose-dependently enhanced the expression of CD80 and CD86 on DCs in vitro, and intravenous or oral administration of glycyrrhizin, an HMGB1 inhibitor, suppressed intestinal DC activation and induction of OVA specific T cell responses, IgA production, and delayed-type hypersensitivity induced by oral CT.
    These results showed that oral CT triggers cell death of IECs and the release of HMGB1 from the damaged IECs, and that the released HMGB1 may mediate antigen sensitization and progression of food allergy.

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  • Activation of dendritic cells and induction of ovalbumin-specific allergic responses by irradiation

    Grant number：24614017  2012.4 - 2015.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    WAKABAYASHI Ayako

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    Authorship：Principal investigator  Grant type：Competitive

    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

    We have observed that dendritic cells (DCs) of the murine intestine were resistance to X-ray irradiation and expression of costimulatory molecule, CD80 on intestinal DCs was enhanced by 10 Gy irradiation although intestinal epithelial cells were sensitive to X-ray irradiation. Then, damage-associated molecular pattern molecule (DAMP) such as HMGB1 was released into culture supernatants when mouse intestinal epithelial cells by organ culture were irradiated with 10-30 Gy. Furthermore, expression of CD80 and CD86 on intestinal DCs was enhanced after addition of HMGB1 in vitro. Thus, we have shown that DAMP such as HMGB1 is released from intestinal epithelial cells damaged by irradiation and intestinal DCs are activated by the released HMGB1. Gut DCs activated by irradiation seem to induce allergic responses and contribute to induction and progression of food allergies.

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  • Induction of ovalbumin-specific allergic reaction by ingestion of food additives including aluminum

    Grant number：21500796  2009.4 - 2011.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    WAKABAYASHI Ayako

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    Authorship：Principal investigator  Grant type：Competitive

    Grant amount：\3640000 （ Direct Cost: \2800000 、 Indirect Cost：\840000 ）

    In this study, we investigated whether the ingestion of aluminum potassium sulfate(APS) in food additives is involved in the triggering and development of allergies. Our research was conducted through animal experimentation and surveys. Oral administration of APS activated dendritic cells in the mesenteric lymph nodes in mice. Furthermore, production of ovalbumin(OVA)-specific antibodies and T cell proliferative responses were enhanced by oral administration of OVA and APS. We also showed that women with allergies consume foods with APS more frequently than woman without allergies. Thus, it was demonstrated that ingestion of APS enhanced immune responses and may contribute to the triggering and development of allergic reactions in mice and humans.

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  • 経口ワクチンによる抗腫瘍免疫誘導法の研究

    2008

    日本医科大学  丸山記念研究助成金 

    若林 あや子

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    Authorship：Principal investigator  Grant type：Competitive

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  • Induction of ovalbumin ?specific immune responses by oral administration of residual chlorine : chlorine and food allergy

    Grant number：18700614  2006.4 - 2008.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)  Grant-in-Aid for Young Scientists (B)

    WAKABAYASHI Ayako

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    Authorship：Principal investigator  Grant type：Competitive

    Grant amount：\3300000 （ Direct Cost: \3000000 、 Indirect Cost：\300000 ）

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  • 腸内の細菌外毒素が卵白アルブミン特異的免疫反応に与える影響:毒素と食物アレルギー

    Grant number：14780079  2002.4 - 2003.3

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    若林 あや子

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    Authorship：Principal investigator  Grant type：Competitive

    Grant amount：\2200000 （ Direct Cost: \2200000 ）

    昨年度は、卵白アルブミン(OVA)と共にコレラ毒素(CT)をマウスに経口投与した場合、OVA特異的なIII型およびIV型アレルギーが著しく誘導されることが示された。本年度は、昨年度に引き続き動物を用いて、コレラ毒素以外の腸内細菌外毒素が、OVAに対するアレルギー反応を引き起こすか否かを検討した。また、食物アレルギーを発症している患者および健常人から採取した血液より血清を分離し、数種類の腸内細菌外毒素について、ELISA法を用いて特異的IgG抗体価を吸光度測定した。実験には、CTの他、緑膿菌のエクソトキシンA、ディフィシル菌のトキシンA、および黄色ブドウ球菌のエンテロトキシンB(SEB)といった、腸内細菌外毒素を用いた。
    その結果、マウスにおいては、SEBをOVAと共に経口投与した場合、OVA特異的な抗IgG1抗体の産生、および脾臓T細胞の増殖反応が観察された。つまり、SEBもCT同様、動物において、OVA特異的なIII型およびIV型アレルギーを誘導することが明らかになった。一方、トキシンA、エクソトキシンAに関しては、アレルギー誘導能は認められなかった。
    また、食物アレルギー患者と健常人の血清において、CT、エクソトキシンA、およびSEBに特異的なIgG抗体が検出された。エクソトキシンA特異的なIgG抗体価においては、食物アレルギー患者群は、健常人群よりも高い値を示した。
    以上より、動物においてはCTとSEBといった腸内細菌外毒素は、OVAに対するIII型およびIV型アレルギーを誘導することが示された。一方、食物アレルギー患者においては、腸内細菌外毒素であるエクソトキシンAに対する免疫反応が高いことから、健常人よりもこの外毒素に曝露されている可能性がある。動物実験および患者血清を用いた本研究より、腸内細菌の外毒素は、食事性タンパク質に対するアレルギー反応の誘導に深く関与することが示唆された。

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Teaching Experience

  • 免疫学各論, 免疫学実習, 細菌学各論, 細菌学実習

    Institution：日本医科大学

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  • 食品衛生学実験

    Institution：日本女子大学

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