Mucosal Immunology and self‐discrimination

2011 Fiscal Year Final Research Report

• Project Area: Immunological Self Recognition and its Disorders
• Project/Area Number: 19059003
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: KIYONO Hiroshi 東京大学, 医科学研究所, 教授 (10271032)
• Co-Investigator(Kenkyū-buntansha): SIDONIA Fagarasan 理化学研究所, 免疫アレルギーセンター科学総合研究センター, チームリーダー (00391970)
• Project Period (FY): 2007 – 2011
• Keywords: 共生細菌 / パイエル板 / Alcaligenes / フコシル化 / IgA / 孤立リンパ濾胞 / M細胞 / Tfh細胞

Research Abstract

In this study, we found some gut commensal bacteria, which habit at the inside of gut-associated lymphoid tissue such as Peyer’s patches. To make a cohabitation niche in the tissue, the mucosal immune system plays a critical role. It was also suggested that a breakdown of symbiotic relationship between host and microbes led to chronic inflammation such as inflammatory bowel diseases. We also demonstrated that a mutual relationship between commensal microbiota, mucosal immunocompetent cells and intestinal epithelial cells strictly regulated a homeostasis of not only mucosal but also systemic immunity.

Research Products

• [Journal Article] Impaired selection of IgA and intestinal dysbiosis associated with PD-1-deficiency (2013)
  • Author(s): Maruya, M., Kawamoto, S., Kato, LM., and Fagarasan, S
  • Journal Title: Gut Microbes Volume: 4(2) Pages: 65-71
• [Journal Article] Nuclear transferred embryonic stem cells for analysis of B1 B-lymphocyte development (2013)
  • Author(s): Takase, M., Iida, R., Maruya, M., Sakaue-Sawano, A., Miyawaki, A., Wakayama, T., Nishigami, S., Fagarasan, S. and Kanagawa O
  • Journal Title: Int Immunol Volume: 25(3) Pages: 145-56
• [Journal Article] The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut (2012)
  • Author(s): Kawamoto, S., Tran, TH., Maruya, M., Suzuki, K., Doi, Y., Tsutsui, Y., Kato, LM., and Fagarasan, S
  • Journal Title: Science. Apr Volume: 336(6080) Pages: 485-9
• [Journal Article] The airway antigen sampling system: Respiratory M cells as an alternative gateway for inhaled antigens (2011)
  • Author(s): Kim, D-Y., Sato, A., Fukuyama, S., Sagara, H, Nagatake, T., Kong, IG., Goda, K., Nochi, T., Kunisawa, J., Sato, S., Yokota, Y., Lee, CH., and Kiyono, H
  • Journal Title: J. Immunol Volume: 186 Pages: 4253-4262
• [Journal Article] Vitamin A-dependent transcriptional activation of the nuclear factor of activated T cells c1 (NFATc1) is critical for the development and survival of B1 cells (2011)
  • Author(s): Maruya M, Suzuki K, Fujimoto H, Miyajima M, Kanagawa O, Wakayama T, and Fagarasan, S
  • Journal Title: Proc Natl Acad Sci U S A Volume: 108(2) Pages: 722-7
• [Journal Article] Epithelial cell microRNAs in gut immunity (2011)
  • Author(s): Goto, Y., and Kiyono, H
  • Journal Title: Nat Immunol Volume: 12 Pages: 195-197
• [Journal Article] Peaceful mutualism in the gut: revealing key commensal bacteria for the creation and maintenance of immunological homeostasis (2011)
  • Author(s): Kunisawa, J., and Kiyono, H
  • Journal Title: Cell Host Microbe Volume: 9 Pages: 83-84
• [Journal Article] Distinct fucosylation of M cells and epithelial cells by Fut1 and Fut2, respectively, in response to intestinal environmental stress (2011)
  • Author(s): Terahara, K., Nochi, T., Yoshida, M., Takahashi, Y., Goto, Y., Hatai, H., Kurokawa, S., Jang, H-M., Kweon, M-N, Domino, SE., Hiroi, T., Yuki, Y., Tsunetsugu-Yokota, Y., Kobayashi, K., and Kiyono, H
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 404 Pages: 822-828
• [Journal Article] Adaptive immune regulation in the gut: T cell-dependent and T cell-independent IgA synthesis (2010)
  • Author(s): Fagarasan, S., Kawamoto, S., Kanagawa, O and Suzuki, K
  • Journal Title: Annu Rev Immunol Volume: 28 Pages: 243-73
• [Journal Article] The sensing of environmental stimuli by follicular dendritic cells promotes immunoglobulin A generation in the gut (2010)
  • Author(s): Suzuki, K., Maruya, M., Kawamoto, S., Sitnik, K., Kitamura, H., Agace, WW and Fagarasan, S
  • Journal Title: Immunity. Jul Volume: 33(1) Pages: 71-83
• [Journal Article] Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines (2010)
  • Author(s): Nochi, T., Yuki, Y., Takahashi, H., Sawada, SI., Mejima, M., Kohda, T., Harada, N., Kong, IG., Sato, A., Kataoka, N., Tokuhara, D., Kurokawa, S., Takahashi, Y., Tsukada, H., Kozaki, S., Akiyoshi, K., and Kiyono, H
  • Journal Title: Nature Mater Volume: 9 Pages: 572-578
• [Journal Article] Secretory IgA-mediated protection against V. cholerae and heat-labile enterotoxin-producing enterotoxigenic Escherichia coli by rice-based vaccine (2010)
  • Author(s): Tokuhara, D., Yuki, Y., Nochi, T., Kodama, T., Mejima, M., Kurokawa, S., Takahashi, Y., Nanno, M., Nakanishi, U., Takaiwa, F., Honda, T., and Kiyono, H
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 107 Pages: 8794-8799
• [Journal Article] Indigenous opportunistic bacteria inhabit mammalian gut-associated lymphoid tissues and share a mucosal antibody-mediated symbiosis (2010)
  • Author(s): Obata, T., Goto, Y., Kunisawa, J., Sato, S., Sakamoto, M., Setoyama, H., Matsuki, T., Nonaka, K., Shibata, N., Gohda, M., Kagiyama, Y., Nochi, T., Yuki, Y., Fukuyama, Y., Mukai, A., Shinzaki, S., Fujihashi, K., Sasakawa, C., Iijima, H., Goto, M., Umesaki, Y., Benno, Y., and Kiyono, H
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 107 Pages: 7419-7424
• [Journal Article] Adaptive immune regulation in the gut: T cell-dependent and T cell-independent IgA synthesis (2010)
  • Author(s): Fagarasan, S. et al.
  • Journal Title: Adv Immunol Volume: 107 Pages: xiii-xiv
• [Journal Article] B cell-specific and stimulation-responsive enhancers derepress (2010)
  • Author(s): Tran, TH., Nakata, M., Suzuki, K., Begum, NA., Shinkura, R., Fagarasan, S. and Honjo, T and Nagaoka H
  • Journal Title: Aicda by overcoming the effects of silencers Volume: 11(2) Pages: 148-54
• [Journal Article] Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer's patches (2009)
  • Author(s): Tsuji, M., Komatsu, N., Kawamoto, S., Suzuki, K., Kanagawa, O., Honjo, T., Hori, S and Fagarasan, S
  • Journal Title: Science Volume: 13;323(5920) Pages: 1488-92
• [Journal Article] Diverse regulatory pathways for IgA synthesis in the gut (2009)
  • Author(s): Suzuki, K., and Fagarasan, S
  • Journal Title: Mucosal Immunol Volume: 2(6) Pages: 468-71
• [Journal Article] A Rice-based oral cholera vaccine induces macaque-specific systemic neutralizing Abs but does not influence pre-existing intestinal immunity (2009)
  • Author(s): Nochi, T., Yuki,Y., Katakai, Y., Shibata, H., Tokuhara,D., Mejima, M., Kurokawa,S., Takahashi,Y., Nakanishi, U., Ono, F., Mimuro, H., Sasakawa, S., Takaiwa, F., Terao, K., and Kiyono, H
  • Journal Title: J. Immunol Volume: 183 Pages: 6538-6544
• [Journal Article] Expression of newly identified secretory CEACAM1(a) isoforms in the intestional epithelium (2009)
  • Author(s): Terahara, K., Yoshida, M., Taguchi, F., Igarashi, O., Nochi, T., Gotoh, Y., Yamamoto, T., Tsunetsugu-Yokota, Y., Beauchemin, N., and Kiyono, H
  • Journal Title: Biochem Biophys Res Commun Volume: 383 Pages: 340-346
• [Journal Article] RANKL is necessary and sufficient to initiate development of antigen-sampling M cells in the intestinal epithelium (2009)
  • Author(s): Knoop, KA., Kumar, N., Butler, BR., Sakthivel, SK., Taylor, RT., Nochi, T., Akiba, H., Yagita, H., Kiyono, H., and Williams, IR
  • Journal Title: J. Immunol Volume: 183 Pages: 5738-5747
• [Journal Article] Uptake through glycoprotein 2 of FimH(+) bacteria by M cells initiates mucosal immune response (2009)
  • Author(s): Hase, K., Kawano, K., Nochi, T., Pontes, GS., Fukuda, S., Ebisawa, M., Kadokura, K., Tobe, T., Fujimura, Y., Kawano, S., Yabashi, A., Waguri, S., Nakato, G., Kimura, S., Murakami, T., Iimura, M., Hamura, K., Fukuoka, S., Lowe, AW., Itoh, K., Kiyono, H., and Ohno, H
  • Journal Title: Nature Volume: 462 Pages: 226-230
• [Journal Article] Mucosal immunosenescence : New developments and vaccines to control infectious diseases (2009)
  • Author(s): Fujihashi, K. and Kiyono, H
  • Journal Title: Trends Immunol Volume: 30 Pages: 334-343
• [Journal Article] Id2-, RORγt-, and LTβR-independent lymphoid organogenesis in ocular immunity (2009)
  • Author(s): Nagatake, T., Fukuyama, S, Kim. D-Y., Goda, K., Igarashi.O., Sato,S., Nochi, T., Sagara, H.,Yokota, Y., Jetten, AM., Kaisho, T., Akira, A., Mimuro, H., Sasakawa, C., Fukui, Y., Fujihashi, K., Akiyama, T., Inoue, J., Penninger, J.M., Kunisawa, J., and Kiyono, H
  • Journal Title: J. Exp. Med Volume: 206 Pages: 2351-2364
• [Journal Article] Peyer's patches are required for intestinal IgA responses to Salmonella (2008)
  • Author(s): Hashizume, T., Togawa, A., Nochi, T., Igarashi, O., Kweon, MN., Kiyono, H. and Yamamoto, M
  • Journal Title: Infect. Immun Volume: 76 Pages: 927-934
• [Journal Article] Colonic patches direct the cross-talk between systemic compartments and large intestine independently of innate immunity (2008)
  • Author(s): Chang, SY., Cha, HR., Uematsu, S., Akira, S., Igarashi, O., Kiyono, H., and Kweon, M-N
  • Journal Title: J. Immunol Volume: 180 Pages: 1609-18
• [Journal Article] Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5 (2008)
  • Author(s): Uematsu, S., Fujimoto, K., Jang, MH., Yang, BG., Jung, YJ., Nishiyama, M., Sato, S., Tsujimura, T., Yamamoto, M., Yokota, Y., Kiyono, H., Miyasaka, M., Ishii, KJ., and Akira, S
  • Journal Title: Nature Immunol Volume: 9 Pages: 769-776
• [Journal Article] Comprehensive gene expression analysis among Peyer's patch M cells, villous M cells and intestinal epithelial cells by DNA microarray analysis (2008)
  • Author(s): Terahara, K., Yoshida, M., Igarashi, O., Nochi, T., Pontes, GS., Hase, K., Ohno, H., Kurokawa, S., Mejima, M., Takayama, N., Yuki, Y., Lowe, AW. and Kiyono, H
  • Journal Title: J. Immunol Volume: 180 Pages: 7840-7846
• [Journal Article] The mucosa: at the frontlines of immunity (2008)
  • Author(s): Fehervari1, Z., and Kiyono, H
  • Journal Title: Trends Immunol Volume: 29 Pages: 503-504
• [Presentation] PD-1 Defeciency Skews the Gut Microbiota by altering the IgA Selection in Gut (2012)
  • Author(s): Fagarasan, S
  • Organizer: The 2012 Spring Conference of the Korean Association of Immunologists
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20120400
• [Presentation] Mucosal Decisions of Mutualisum and Elimination for Surface barrier system (2012)
  • Author(s): Invited Speaker
  • Organizer: The 6^<th> Annual International Symposium in Institute of Dermatological Science(IDS)
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20120200
• [Presentation] The Mucosal Gateway System for Antigen-sampling and Homestatic Niche (2011)
  • Author(s): Invited Speaker
  • Organizer: The 15^<th> International Congress of Mucosal Immunology
  • Place of Presentation: Paris, France
  • Year and Date: 20110700
• [Presentation] Intra-Tissue Habitation of Commensal Bacteria in Peyer's patches for Gut Immunity (2010)
  • Author(s): Invited Speaker
  • Organizer: The 8^<th> German-Japanease International Symposium, Regulation of Immune Response and Diseases
  • Place of Presentation: Cuxhahen, Germany
  • Year and Date: 20100900
• [Presentation] Mucosal Decision of Immunity and Tolerance (2010)
  • Author(s): Invited Speaker
  • Organizer: The 83^<rd> Annunal Meeting of Japanese Society for Bacteriology
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 20100300
• [Presentation] T-dependent and T-independent IgA responses in the gut (2009)
  • Organizer: Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: Osaka
  • Year and Date: 20091200
• [Presentation] Session 1"Id2, RORγt, and LTβR independent initiation of TALT genesis in ocular immunity."and Session 2" Indigenous Opportunistic Bacteria Inhabit Mammalian Gut-associated Lymphoid Tissues for Gut Immunity" (2009)
  • Organizer: Trudeau Institute Mucosal Immunology Workshop
  • Place of Presentation: New York, USA
  • Year and Date: 20091000
• [Presentation] T-dependent and T-independent IgA responses in the gut (2009)
  • Organizer: Microanatomy of the Immune Responses in Health and Disease
  • Place of Presentation: University of Birmingham, UK
  • Year and Date: 20090900
• [Presentation] Development of Intestinal Symbiosis by the Mucosal Immune System (2009)
  • Author(s): Invited Speaker
  • Organizer: The 63^<th> Japanese Society for Bacteriology Tohoku District Research Conference
  • Place of Presentation: Morioka, Japan
  • Year and Date: 20090800
• [Presentation] The Mucosal Immune System for the Creation of Gut Symbiosis (2009)
  • Organizer: The 91^<st> Japanese Association of Gastroenteology, Chugoku Division Meeting
  • Place of Presentation: Okayama, Japan
  • Year and Date: 20090600
• [Presentation] Mucosal Decision of Immunity and Tolerance for Creation of Symbiosis (2009)
  • Author(s): Invited Speaker
  • Organizer: The 6^<th> Extraordinary International Symposium on Recent Advances in Otitis Media
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20090500
• [Book] 臨床粘膜免疫学
  • Author(s): 清野宏
  • Publisher: (株)シナジー