Host-microbe interaction mediated by intestinal M cells

• Project/Area Number: 25293114
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Keio University (2014-2015); The University of Tokyo (2013)
• Principal Investigator: Hase Koji 慶應義塾大学, 薬学部, 教授 (20359714)
• Co-Investigator(Renkei-kenkyūsha): MIMURO Hitomi 東京大学, 医科学研究所, 准教授 (80396887) ; FURUSAWA Yukihiro 富山県立大学, 工学部, 講師 (80632306) ; KIMURA Shunsuke 北海道大学, 医学研究科, 助教 (40444525)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2013: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: 粘膜免疫 / M細胞 / 粘膜免疫学 / Ｍ細胞 / パイエル板

Outline of Final Research Achievements

It remains unknown whether M-dependent antigen uptake also contributes to cellular immunity against mucosal pathogens. Here we investigated the contribution of M cells to Th17-dependent cellular immunity. Wild type (WT) and M-cell-null mice were orally infected with Citrobacter rodentium. After the infection, M-cell-null mice developed more severe infectious colitis compared to WT mice, as evidenced by exacerbation of body weight loss and fecal clinical scores. Importantly, colonic Th17 cells were decreased in M-cell-null mice compared to WT mice at the early phase of infection. In contrast, under the physiological conditions, there was no significant difference in the number of colonic Th17 cells between the two groups. Collectively, these results suggested that M-cell-dependent antigen uptake plays a key role in the protection against C. rodentium infection by facilitating antigen-specific Th17 induction.

Research Products

• [Journal Article] The diet-microbiota-metabolite axis regulates the host physiology. (2016)
  • Author(s): Yamada T, Takahashi D, Hase K.
  • Journal Title: J. Biochem. Volume: in press Issue: 1 Pages: 1-10
  • DOI: 10.1093/jb/mvw022
  • NAID: 40020880708
  • Peer Reviewed
• [Journal Article] Epithelium-Intrinsic MicroRNAs Contribute to Mucosal Immune Homeostasis by Promoting M-Cell Maturation. (2016)
  • Author(s): Nakato G, Hase K, Sato T, Kimura S, Sakakibara S, Sugiyama M, Obata Y,Hanazato M, Iwanaga T, Ohno H.
  • Journal Title: PLoS One Volume: 11 Issue: 3 Pages: e0150379-e0150379
  • DOI: 10.1371/journal.pone.0150379
  • Peer Reviewed / Open Access
• [Journal Article] EAF2 mediates germinal centre B-cell apoptosis to suppress excessive immune responses and prevent autoimmunity (2016)
  • Author(s): 1.Li, Y., Takahashi, Y., Fujii, S., Zhou, Y., Hong, R., Suzuki, A., Tsubata, T., Hase, K., Wang, J.-Y.
  • Journal Title: Nature Commun. Volume: 7 Issue: 1 Pages: 1-13
  • DOI: 10.1038/ncomms10836
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Epigenetic modifications of the immune system in health and disease (2015)
  • Author(s): Yuuki Obata, Yukihiro Furusawa and Koji Hase.
  • Journal Title: Immunology and Cell Biology Volume: 93 Issue: 3 Pages: 226-232
  • DOI: 10.1038/icb.2014.114
  • Peer Reviewed
• [Journal Article] Visualization of the entire differentiation process of murine M cells : suppression of their maturation in cecal patches. (2015)
  • Author(s): Shunsuke Kimura, Megumi Yamakami-Kimura, Yuuki Obata, Koji Hase, Hiroshi Kitamura, Hiroshi Ohno and Toshihiko Iwanaga.
  • Journal Title: Mucosal Immunol. Volume: 8 Issue: 3 Pages: 650-660
  • DOI: 10.1038/mi.2014.99
  • Peer Reviewed
• [Journal Article] Commensal microbiota regulates T cell fate decision in the gut (2014)
  • Author(s): Yukihiro Furusawa, Yuuki Obata and Koji Hase.
  • Journal Title: Seminars in Immunopathology Volume: 37 Issue: 1 Pages: 017-025
  • DOI: 10.1007/s00281-014-0455-3
  • Peer Reviewed
• [Journal Article] Epithelial-stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues (2014)
  • Author(s): Yuuki Obata, Shunsuke Kimura, Gaku Nakato, Keito Iizuka, Yurika Miyagawa, Yutaka Nakamura, Yukihiro Furusawa, Machiko Sugiyama, Keiichiro Suzuki, Masashi Ebisawa, Yumiko Fujimura, Hisahiro Yoshida, Toshihiko Iwanaga, Koji Hase and Hiroshi Ohno.
  • Journal Title: EMBO Reports Volume: 12 Issue: 12 Pages: 1297-1304
  • DOI: 10.15252/embr.201438942
  • Peer Reviewed
• [Journal Article] The epigenetic regulator Uhrf1 facilitates proliferation and maturation of colonic regulatory T cells (2014)
  • Author(s): Yuuki Obata*, Yukihiro Furusawa*, Takaho A. Endo, Jafar Sharif, Daisuke Takahashi, Koji Atarashi, Manabu Nakayama, Satoshi Onawa, Yumiko Fujimura, Masumi Takahashi, Tomokatsu Ikawa, Takeshi Otsubo, Yuki I. Kawamura, Taeko Dohi, Shoji Tajima, Osamu Ohara, Kenya Honda, Shohei Hori, Hiroshi Ohno, Haruhiko Koseki and Koji Hase. 【* : 筆頭筆者】
  • Journal Title: Nature Immunology Volume: 15 Issue: 6 Pages: 571-579
  • DOI: 10.1038/ni.2886
  • Peer Reviewed / Open Access
• [Journal Article] Commensal microbe-derived butyrate induces colonic regulatory T cells (2013)
  • Author(s): Yukihiro Furusawa, Yuuki Obata, Shinji Fukuda, Takaho A. Endo, Gaku Nakato, Daisuke Takahashi, Yumiko Nakanishi, Chikako Uetake, Keiko Kato, Tamotsu Kato, Masumi Takahashi, Noriko N. Fukuda, Shinnosuke Murakami, Eiji Miyauchi, Shingo Hino, Koji Atarashi, Satoshi Onawa, Yumiko Fujimura, Trevor Lockett, Julie M. Clarke, David L. Topping, Masaru Tomita, Shohei Hori, Osamu Ohara, Tatsuya Morita, Haruhiko Koseki, J un Kikuchi, Kenya Honda, Koji Hase and Hiroshi Ohno
  • Journal Title: Nature Volume: 506 Issue: 7480 Pages: 446-450
  • DOI: 10.1038/nature12721
  • Peer Reviewed
• [Journal Article] Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota (2013)
  • Author(s): Koji Atarashi, Takeshi Tanoue, et al.
  • Journal Title: Nature Volume: 500 Issue: 7461 Pages: 232-236
  • DOI: 10.1038/nature12331
  • Peer Reviewed
• [Journal Article] AP-1B-Mediated Protein Sorting Regulates Polarity and Proliferation of Intestinal Epithelial Cells in Mice (2013)
  • Author(s): Koji Hase, Fubito Nakatsu, Masumi Ohmae, Kahushi Sugihara, Noriko Shioda, Daisuke Takahashi, Yuuki Obata, Yukihiro Furusawa, Yumiko Fujimura, Taisuke Yamashita, Shinji Fukuda, Hiroshi Okamoto, Masahide Asano, Shigenobu Yonemura and Hiroshi Ohno.
  • Journal Title: Gastroenterology Volume: 145 Issue: 3 Pages: 625-635
  • DOI: 10.1053/j.gastro.2013.05.013
  • Peer Reviewed
• [Journal Article] Ubiquitin-specific protease 2-69 in macrophages potentially modulates metainflammation. (2013)
  • Author(s): Kitamura et al.
  • Journal Title: FASEB J. Volume: 27 Issue: 12 Pages: 4940-4953
  • DOI: 10.1096/fj.13-233528
  • Peer Reviewed
• [Presentation] Biological significance of intestinal M cells (2015)
  • Author(s): Nakamura Y, Hase K et al.
  • Organizer: The 44th Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: Sapporo Convention Center, Sapporo, Japan
  • Year and Date: 2015-11-18
• [Presentation] Symbiotic microorganisms regulate host physiology via interkingdom signaling (2015)
  • Author(s): Hase K.
  • Organizer: The 12th Japanese-German Frontiers of Science (JGFoS) Symposium
  • Place of Presentation: Kyoto Brighton Hotel, Kyoto, Japan
  • Year and Date: 2015-10-01
  • Int'l Joint Research / Invited
• [Presentation] Commensal bacteria shape gut immune system through epigenetic modifications. (2014)
  • Author(s): Hase K.
  • Organizer: The Fourth International Conference on Regulatory T Cells and Th Subsets and Clinical Application in Human Diseases.
  • Place of Presentation: Shanghai, China
  • Year and Date: 2014-11-01 – 2014-11-04
  • Invited
• [Presentation] Commensal bacteria shape the intestinal immune system through epigenetic modifications. (2014)
  • Author(s): Hase K. et al.
  • Organizer: International Conference of KSMCB
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2014-10-23
  • Invited
• [Presentation] Intestinal microbiota shapes epithelial barriers & gut immune system. (2014)
  • Author(s): Hase K.
  • Organizer: 第87回日本生化学会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-01
  • Invited
• [Presentation] 腸内細菌による免疫エピゲノム修飾機構の解明 (2014)
  • Author(s): 長谷耕二
  • Organizer: 第38回阿蘇シンポジウム
  • Place of Presentation: 阿蘇
  • Year and Date: 2014-07-25 – 2014-07-26
  • Invited
• [Presentation] 酪酸エステル難消化性でんぷんを用いた粘膜免疫系のエピジェネティクス制御. (2014)
  • Author(s): 長谷耕二
  • Organizer: 第68回日本栄養食糧学会
  • Place of Presentation: 札幌
  • Year and Date: 2014-06-02
  • Invited
• [Presentation] Commensal microbiota shapes the gut immune system through epigenetic modifications. (2014)
  • Author(s): Hase K.
  • Organizer: Digestive Disease Week 2014. AGA-JSGE Joint Symposium.
  • Place of Presentation: Chicago, USA
  • Year and Date: 2014-05-04 – 2014-05-06
  • Invited
• [Presentation] Epigenetic machineries facilitate mutualistic immune adaptation to microbial colonization in the gut. (2014)
  • Author(s): Hase K.
  • Organizer: 109th Titisee Conference
  • Place of Presentation: Titisee, Germanay
  • Year and Date: 2014-04-09 – 2014-04-13
  • Invited
• [Presentation] 腸内細菌由来の代謝産物による免疫バリア修飾作用 (2014)
  • Author(s): 長谷耕二
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
  • Invited
• [Presentation] A commensal microbe-derived short-chain fatty acid epigenetically induces colonic regulatory T cells. (2013)
  • Author(s): Yukihiro Furusawa, Yuuki Obata and Koji Hase
  • Organizer: The 12th Awaji International Forum on Infection & Immunity.
  • Place of Presentation: Awaji, Japan
  • Invited
• [Presentation] 腸内発酵産物による粘膜免疫修飾作用 (2013)
  • Author(s): 長谷耕二
  • Organizer: 第67回日本栄養・食糧学会大会
  • Place of Presentation: 名古屋
  • Invited
• [Presentation] Commensal microbiota shapes the gut immune system through epigenetic modifications (2013)
  • Author(s): Koji Hase
  • Organizer: The 8th RCAI-JSI International Symposium on Immunology 2013
  • Place of Presentation: Ykohama, Japan
  • Invited
• [Presentation] 腸内発酵産物による粘膜免疫系のエピジェネティクス制御 (2013)
  • Author(s): 長谷耕二
  • Organizer: 日本食品免疫学会第9回学術大会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 上皮特異的膜輸送因子AP-1Bによる腸上皮バリア形成とその破綻による大腸炎発症メカニズム. (2013)
  • Author(s): 長谷耕二
  • Organizer: 日本膜学会第35年会
  • Place of Presentation: 東京
  • Invited