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Differentiation and function of M cells, a unique intestinal epithelial cell subset for untigen uptake

Research Project

Project/Area Number 16H05207
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Ohno Hiroshi  国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (50233226)

Co-Investigator(Kenkyū-buntansha) 金谷 高史  国立研究開発法人理化学研究所, 生命医科学研究センター, 上級研究員 (20553829)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2016: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
Keywords腸管免疫系 / 腸管関連リンパ組織 / M細胞 / 濾胞関連上皮 / RANKL / NF-kB / IL-22 / 食物抗原 / Spi-B / IL-22BP / 免疫学 / M細胞 / 細菌 / GALT / 濾胞関連上皮(FAE) / NFkB / 遺伝子欠損マウス / RANK / 抗菌ペプチド
Outline of Final Research Achievements

We have found that both NFkB canonical and noncanonical pathways are required, and that the transcription factor SpiB is necessary but not sufficient, for M-cell differentiation .
We found that M cell-specific surface molecule Umod acts as an uptake receptor for Lactobacillus acidophilus expressing SlpA. We also established the monolayer culture of enteroids with M-cell induction.
We have established “antigen-free” mice colony and found that fecal IgA was profoundly decreased in these mice, concomitant with marked reduction in the number of Pyer’s patch B cells and germinal center formation.

Academic Significance and Societal Importance of the Research Achievements

本研究は、M細胞の分化や機能の基礎研究であるが、その成果はM細胞を介する経粘膜感染症・食物アレルギーの効果的なワクチン送達法の開発といった医学研究・応用研究へと発展する可能性がある。したがって最終的には、M細胞を標的とする新たな粘膜ワクチン開発や、食物アレルギーに対する特異的経口免疫寛容誘導などの臨床応用へと繋がり、国民の健康にも貢献できると考えられることから、医療経済的、社会的にも意義深いと考える。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (22 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 7 results) Presentation (7 results) (of which Invited: 3 results) Remarks (6 results)

  • [Int'l Joint Research] Emory University/New York University(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Sox8 is essential for M cell maturation to accelerate IgA response at the early stage after weaning in mice2019

    • Author(s)
      Kimura Shunsuke、Kobayashi Nobuhide、Nakamura Yutaka、Kanaya Takashi、Takahashi Daisuke、Fujiki Ryoji、Mutoh Mami、Obata Yuuki、Iwanaga Toshihiko、Nakagawa Tomoo、Kato Naoya、Sato Shintaro、Kaisho Tsuneyasu、Ohno Hiroshi、Hase Koji
    • Journal Title

      The Journal of Experimental Medicine

      Volume: 216 Issue: 4 Pages: 831-846

    • DOI

      10.1084/jem.20181604

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling.2018

    • Author(s)
      Kanaya T, Sakakibara S, Jinnohara T, Hachisuka M, Tachibana N, Hidano S, Kobayashi T, Kimura S, Iwanaga T, Nakagawa T, Katsuno T, Kato N, Akiyama T, Sato T, Williams IR, Ohno H.
    • Journal Title

      J Exp Med.

      Volume: 5;215(2) Issue: 2 Pages: 501-519

    • DOI

      10.1084/jem.20160659

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] NALT M cells are important for immune induction for the common mucosal immune system.2017

    • Author(s)
      Date Y, Ebisawa M, Fukuda S, Shima H, Obata Y, Takahashi D, Kato T, Hanazato M, Nakato G, Williams IR, Hase K, Ohno H.
    • Journal Title

      Int. Immunol.

      Volume: 29 Issue: 10 Pages: 471-478

    • DOI

      10.1093/intimm/dxx064

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Uromodulin-SlpA binding dictates Lactobacillus acidophilus uptake by intestinal epithelial M cells.2017

    • Author(s)
      Yanagihara S, Kanaya T, Fukuda S, Nakato G, Hanazato M, Wu XR, Yamamoto N, Ohno H.
    • Journal Title

      Int. Immunol.

      Volume: 29 Issue: 8 Pages: 357-363

    • DOI

      10.1093/intimm/dxx043

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] IL-22BP dictates characteristics of Peyer's patch follicle-associated epithelium for antigen uptake.2017

    • Author(s)
      Jinnohara T, Kanaya T, Hase K, Sakakibara S, Kato T, Tachibana N, Sasaki T, Hashimoto Y, Sato T, Watarai H, Kunisawa J, Shibata N, Williams I, Kiyono H, and Ohno H.
    • Journal Title

      J. Exp. Med.

      Volume: 214 Issue: 6 Pages: 1607-1618

    • DOI

      10.1084/jem.20160770

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distinct Roles for the N- and C-terminal Regions of M-Sec in Plasma Membrane Deformation during Tunneling Nanotube Formation.2016

    • Author(s)
      Kimura S, Yamashita M, Yamakami-Kimura M, Sato Y, Yamagata A, Kobashigawa Y, Inagaki F, Amada T, Hase K, Iwanaga T, Ohno H, Fukai S.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 33548-33548

    • DOI

      10.1038/srep33548

    • NAID

      120005855947

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High-affinity monoclonal IgA regulates gut microbiota and prevents colitis in mice.2016

    • Author(s)
      Okai S, Usui F, Yokota S, Hori-I Y, Hasegawa M, Nakamura T, Kurosawa M, Okada S, Yamamoto K, Nishiyama E, Mori H, Yamada T, Kurokawa K, Matsumoto S, Nanno M, Naito T, Watanabe Y, Kato T, Miyauchi E, Ohno H, Shinkura R.
    • Journal Title

      Nature Microbiology

      Volume: 1 Issue: 9 Pages: 16103-16103

    • DOI

      10.1038/nmicrobiol.2016.103

    • NAID

      120005818448

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [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

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 腸管免疫を発動するM細胞の分化機構に関する研究2018

    • Author(s)
      金谷高史
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Characteristics of M cells and follicle-associated epithelium2017

    • Author(s)
      Ohno, H., Kanaya, T.
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] IL-22 binding protein (IL-22BP) regulates the properties of follicleassociated epithelium (FAE) to facilitate antigen uptake into Peyer's patches2017

    • Author(s)
      Kanayak T., Jinnohara, T., Hase, K., Sasaki, T., Watarai, H., Shibata, N., Kuniswa, J., Kiyono, H., Ohno, H.
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Lactobacillus acidophilus L-92株の小腸パイエル板の M細胞からの取り込みに関与する生体分子の探索2017

    • Author(s)
      柳原 沙恵, 金谷 高史, 弘田 辰彦, 山本 直之, 大野 博司
    • Organizer
      第13回日本食品免疫学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The function of M cells in host-microbe interaction2017

    • Author(s)
      Ohno, H
    • Organizer
      Symposium 207 Gut Microbiome and Mucosal or Systemic Dysfunction Mechanisms, Clinical Manifenstations and Intervention
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Lactobacillus acidophilus L-92株の表層蛋白質が小腸パイエル板のM細胞からの取り込みに与える影響2016

    • Author(s)
      柳原沙恵、福田真嗣、金谷高史、弘田辰彦、山本直之、大野博司
    • Organizer
      日本乳酸菌学会2016年度大会
    • Place of Presentation
      北里大学白金キャンパスコンベンションホール(東京都・港区)
    • Year and Date
      2016-07-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] 腸管免疫とM細胞2016

    • Author(s)
      大野博司
    • Organizer
      第40 回日本リンパ学会総会
    • Place of Presentation
      東京大学伊藤国際学術研究センター(東京都・文京区)
    • Year and Date
      2016-06-24
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Remarks] 理化学研究所生命医科学研究センター粘膜システム研究チーム

    • URL

      http://www.riken.jp/research/labs/ims/intest_ecosys/

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
  • [Remarks] Laboratory for Intestinal Ecosystem, RIKEN IMS h

    • URL

      http://www.riken.jp/en/research/labs/ims/intest_ecosys/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 理化学研究所生命医科学研究センター粘膜システム研究チーム

    • URL

      http://leib.rcai.riken.jp/riken/index.html

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
  • [Remarks] Laboratory for Intestinal Ecosystem, RIKEN IMS

    • URL

      http://www.riken.jp/en/research/labs/ims/intest_ecosys/

    • Related Report
      2017 Annual Research Report
  • [Remarks]

    • URL

      http://www.riken.jp/research/labs/ims/intest_ecosys/

    • Related Report
      2016 Annual Research Report
  • [Remarks]

    • URL

      http://leib.rcai.riken.jp/riken/index.html

    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2022-05-20  

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