Comprehensive understanding of a unique intestinal epithelial M cells specialized for luminal particulate antigen uptake

• Project/Area Number: 24249029
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: OHNO Hiroshi 独立行政法人理化学研究所, 統合生命医科学研究センター, グループディレクター (50233226)
• Co-Investigator(Kenkyū-buntansha): KANATA Takashi 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 研究員 (20553829) ; NAKATO Gaku 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 特別研究員 (20584535)
• Project Period (FY): 2012-05-31 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥46,540,000 (Direct Cost: ¥35,800,000、Indirect Cost: ¥10,740,000); Fiscal Year 2014: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000); Fiscal Year 2013: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000); Fiscal Year 2012: ¥24,830,000 (Direct Cost: ¥19,100,000、Indirect Cost: ¥5,730,000)
• Keywords: 粘膜免疫学 / 細胞・組織 / 発生・分化 / 上皮細胞 / M細胞 / シグナル伝達 / 腸内細菌 / 細菌感染 / 免疫学 / RANKL / NFκB / 分化 / Spi-B / GP2 / サルモネラ / 腸管免疫

Outline of Final Research Achievements

Analysis of Spi-B KO mice have revealed that RANKL-signaling in immature intestinal epithelial cells induces the expression of Spi-B transcription factor, which is prerequisite for subsequent M-cell differentiation. We have further elucidated that both canonical and non-canonical NFκB pathways downstream of RANKL-RANKL signaling is required for M-cell differentiation.
We have also shown that terminally differentiated M cells are fewer in cecal patches compared to Peyer’s patched, and that this is due to the lower expression of RelB, a molecule of the non-canonical NFκB pathway, in cecal patches than in Peyer’s patches.

Research Products

• [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] Botulinum toxin A complex exploits intestinalM cells to enter the host and exert neurotoxicity. (2015)
  • Author(s): Matsumura, T., Sugawara, Y., Yutani, M., Amatsu, S., Yagita, H., Kohda, T., Fukuoka, S.-I., Nakamura, Y., Fukuda, S., Hase, K., Ohno, H., Fujinaga, Y.
  • Journal Title: Nat. Commun. Volume: 6 Issue: 1 Pages: 6255-6255
  • DOI: 10.1038/ncomms7255
  • Peer Reviewed / Open Access
• [Journal Article] A novel mucosal vaccine targeting Peyer's patch M cells induces protective antigen-specific IgA responses (2014)
  • Author(s): Shima, H., Watanabe, T., Fukuda, S., Fukuoka, S. I., Ohara, O., Ohno, H
  • Journal Title: Int. Imunol. Volume: 26 Issue: 11 Pages: 619-625
  • DOI: 10.1093/intimm/dxu061
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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] <i>Lactobacillus acidophilus</i> L-92 Cells Activate Expression of Immunomodulatory Genes in THP-1 Cells (2014)
  • Author(s): Yanagihara, S., Goto, H., Hirota, T., Fukuda, S., Ohno, H., Yamamoto, N.
  • Journal Title: Bioscience of Microbiota, Food and Health Volume: 33 Issue: 4 Pages: 157-164
  • DOI: 10.12938/bmfh.33.157
  • NAID: 130004680094
  • ISSN: 2186-3342
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Selection of an Aptamer against Mouse GP2 by SELEX (2014)
  • Author(s): Hanazato, M., Nakato, G., Nishikawa, F., Hase, K., Nishikawa, S., Ohno, H.
  • Journal Title: Cell Structure and Function Volume: 39 Issue: 1 Pages: 23-29
  • DOI: 10.1247/csf.13019
  • NAID: 130004053898
  • ISSN: 0386-7196, 1347-3700
  • Peer Reviewed
• [Journal Article] The functional maturation of M cells is dramatically reduced in the Peyer's patches of aged mice. (2013)
  • Author(s): Kobayashi, A., Donaldson, D. S., Erridge, C., Kanaya, T., Williams, I. R., Ohno, H., Mahajan, A., Mabbott, N. A.
  • Journal Title: Mucosal Immunol. Volume: 6 Issue: 4 Pages: 1027-1037
  • DOI: 10.1038/mi.2013.30
  • Peer Reviewed
• [Journal Article] Distinct Roles for CXCR6+ and CXCR6- CD4+ T Cells in the Pathogenesis of Chronic Colitis (2013)
  • Author(s): Mandai Y, Takahashi D, Hase K, Obata Y, Furusawa Y, Ebisawa M, Nakagawa T, Sato T, Katsuno T, Saito Y, Shimaoka T, Yokosuka O, Yokote K, Ohno H
  • Journal Title: PloS One Volume: 8(6) Issue: 6 Pages: e65488-e65488
  • DOI: 10.1371/journal.pone.0065488
  • Peer Reviewed
• [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] The Ets transcription factor Spi-B is essential for the differentiation of intestinal microfold cells (2012)
  • Author(s): Kanaya, T., Hase, K., Takahashi, D., Fukuda, S., Hoshino, K., Sasaki, I., Hemmi, H., Knoop, K. A., Kumar, N., Sato, M., Katsuno, T., Yokosuka, O., Toyooka, K., Nakai, K., Sakamoto, A., Kitahara, Y., Jinnohara, T., McSorley, S. J., Kaisho, T., Williams, I. R., and Ohno, H.
  • Journal Title: Nat Immunol Volume: 13 Issue: 8 Pages: 729-736
  • DOI: 10.1038/ni.2352
  • Peer Reviewed
• [Journal Article] Brucella abortus exploits a cellular prion protein on intestinal M cells as an invasive receptor. (2012)
  • Author(s): Nakato G, Hase K, Suzuki M, Kimura M, Ato M, Hanazato M, Tobiume M, Horiuchi M, Atarashi R, Nishida N, Watarai M, Imaoka K, Ohno H
  • Journal Title: Journal of Immunology Volume: 189(4) Issue: 4 Pages: 1540-4
  • DOI: 10.4049/jimmunol.1103332
  • Peer Reviewed
• [Journal Article] Identification of novel genes selectively expressed in the follicle-associated epithelium from the meta-analysis of transcriptomics data from multiple mouse cell and tissue populations. (2012)
  • Author(s): Kobayashi A, Donaldson DS, Kanaya T, Fukuda S, Baillie JK, Freeman TC, Ohno H, Williams IR, Mabbott NA.
  • Journal Title: DNA Res. Volume: 19(5) Issue: 5 Pages: 407-22
  • DOI: 10.1093/dnares/dss022
  • Peer Reviewed
• [Journal Article] The functional maturation of M cells is dramatically reduced in the Peyer's patches of aged mice. (2012)
  • Author(s): Kobayashi Atsushi
  • Journal Title: Mucosal Immunol. Volume: 印刷中 Issue: 5 Pages: 1027-1037
  • DOI: 10.1038/mi.2012.141
  • Peer Reviewed
• [Journal Article] M cell-depletion blocks oral prion disease pathogenesis (2011)
  • Author(s): Donaldson, D.S., et al
  • Journal Title: Mucosal Immunol Volume: 5 Issue: 2 Pages: 216-225
  • DOI: 10.1038/mi.2011.68
  • Peer Reviewed
• [Presentation] Function and differentiation of M cells, a unique subset of intestinal epithelium for antigen-uptake (2015)
  • Author(s): Ohno H
  • Organizer: 第88回日本細菌学会 （International Symposium)
  • Place of Presentation: 岐阜県岐阜市・長良川国際会議場
  • Year and Date: 2015-03-26 – 2015-03-28
  • Invited
• [Presentation] Host-Gut Microbial Communication in Host Defense and Immunity (2015)
  • Author(s): Ohno H
  • Organizer: The Microbiome Forum: Asia
  • Place of Presentation: Kuala Lumpur, Malaysia
  • Year and Date: 2015-03-19 – 2015-03-20
  • Invited
• [Presentation] Gut microbiome in the host defense and gut immune regulation (2015)
  • Author(s): Ohno H
  • Organizer: 16th Congress of the Korean Scoiety of Surgical Metabolism and Nutrition & 2015 International Symposium
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2015-03-13 – 2015-03-14
  • Invited
• [Presentation] 腸エコシステムと疾患・生体防御 (2014)
  • Author(s): 大野博司
  • Organizer: 第３５回日本肥満学会 (教育講演)
  • Place of Presentation: 宮崎県宮崎市・シーガイアコンベンションセンター
  • Year and Date: 2014-10-24 – 2015-10-25
  • Invited
• [Presentation] 腸内フローラと生体防御・免疫系 ：統合オミクス手法によるアプローチ (2014)
  • Author(s): 大野博司
  • Organizer: 第４６回日本小児感染症学会学術集会 （特別講演）
  • Place of Presentation: 東京都新宿区・京王プラザホテル
  • Year and Date: 2014-10-18 – 2014-10-19
  • Invited
• [Presentation] 食品・腸内細菌と生体防御・腸管免疫系 (2014)
  • Author(s): 大野博司
  • Organizer: 日本食品免疫学会設立１０周年記念学術大会
  • Place of Presentation: 東京都文京区・東京大学伊藤謝恩ホール
  • Year and Date: 2014-10-16 – 2014-10-17
  • Invited
• [Presentation] 宿主-腸内フローラ相互作用 (2014)
  • Author(s): 大野博司
  • Organizer: 第３５回日本食品微生物学会学術集会（教育講演）
  • Place of Presentation: 大阪府堺市・大阪府立大学中百舌鳥キャンパス
  • Year and Date: 2014-09-18 – 2014-09-19
  • Invited
• [Presentation] Gut microbe-derived butyrate can induce colonic Treg differentiation (2014)
  • Author(s): Ohno H
  • Organizer: Cold Spring Harbor Conferences Asia 2014: Frontiers of Immunology in Health & Diseases
  • Place of Presentation: Suzhou, China
  • Year and Date: 2014-09-02 – 2014-09-06
  • Invited
• [Presentation] 統合オミクス手法による宿主―腸内フローラ相互作用の解析 (2014)
  • Author(s): 大野博司
  • Organizer: 第46回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 東京都新宿区・京王プラザホテル
  • Year and Date: 2014-07-10 – 2014-07-11
  • Invited
• [Presentation] Integrative multi-omics approach for analyzing gut ecosystem (2014)
  • Author(s): Ohno H
  • Organizer: 第18回腸内細菌学会 （International Symposium)
  • Place of Presentation: 東京都文京区・東京大学伊藤国際学術研究センター
  • Year and Date: 2014-06-11 – 2014-06-12
  • Invited
• [Presentation] 腸内細菌と代謝調節 (2014)
  • Author(s): 大野博司
  • Organizer: 第８７回日本内分泌学会学術総会 （教育講演）
  • Place of Presentation: 福岡県福岡市・福岡国際会議場・福岡サンパレス
  • Year and Date: 2014-04-24 – 2014-04-26
  • Invited
• [Presentation] The role of M cells in intestinal helminthic infection (2013)
  • Author(s): Chikako Shimokawa, Takashi Kanaya, Tsuneyasu Kaisho, Hiroshi Ohno
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉県千葉市
• [Presentation] 腸内細菌と疾患 (2013)
  • Author(s): 大野博司
  • Organizer: 第86回日本内分泌学会学術総会
  • Place of Presentation: 宮城県仙台市
  • Invited
• [Presentation] Differentiation and function of M cells, a unique subset of intestinal epithelial cells specialized for mucosal antigen-uptake (2013)
  • Author(s): Ohno, H.
  • Organizer: The American Association of Immunologists Annual Meeting
  • Place of Presentation: Honolulu, Hawaii, USA
  • Invited
• [Presentation] Differentiation and function of M cells, a unique subset of intestinal epithelial cells specialized for mucosal antigen-uptake (2013)
  • Author(s): Ohno, H.
  • Organizer: 16th International Congress of Mucosal Immunology
  • Place of Presentation: Vancouver, Canada
  • Invited
• [Presentation] Antigen delivery to the gut immune system through epithelium: M cells vs FAE? (2012)
  • Author(s): Ohno, H
  • Organizer: Gordon Research Conference, Lysosomes & Endocytosis
  • Place of Presentation: Andover, NH, USA
  • Invited
• [Presentation] M cells, a unique subset of intestinal epithelial cells specialized for mucosal antigen-uptake (2012)
  • Author(s): Ohno, H
  • Organizer: M cells, a unique subset of intestinal epithelial cells specialized for mucosal antigen-uptake
  • Place of Presentation: 淡路島、兵庫
  • Invited
• [Presentation] Function and differentiation of M cells, a unique subset of intestinal epithelial cells specialized for mucosal antigen-uptake (2012)
  • Author(s): Ohno,H
  • Organizer: The 12th International Symposium on Dendritic Cells
  • Place of Presentation: Daegu, Korea
  • Invited
• [Remarks] 理化学研究所統合生命医科学研究センター粘膜システム研究グループ
  • URL: http://www.riken.jp/research/labs/ims/intest_ecosys/
• [Remarks] 理化学研究所統合生命医科学研究センター粘膜システム研究グループ
  • URL: http://leib.rcai.riken.jp/riken/index.html
• [Remarks] 理化学研究所統合生命医科学研究センター粘膜システム研究グループ
  • URL: http://leib.rcai.riken.jp/riken/index.html
• [Remarks] 所属機関ホームページ
  • URL: http://www.ims.riken.jp/
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