Regulation of mucosal immune system by polarized sorting in epithelial cells

2012 Fiscal Year Final Research Report

• Project Area: Intracellular logistics: interdisciplinary approaches to pathophysiology of membrane traffic
• Project/Area Number: 20113003
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• 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, 免疫系構築研究チーム, チームリーダー (50233226)
• Co-Investigator(Kenkyū-buntansha): KIMURA Shunsuke 北海道大学, 医学研究科, 助教 (40444525)
• Project Period (FY): 2008 – 2012
• Keywords: 細胞内ロジスティクス / 上皮細胞極性輸送 / AP-1B / GP2 / M-Sec / 粘膜免疫系

Research Abstract

We have studied the regulation of mucosal immune system by polarized sorting in epithelial cells using AP-1B, M-cell-specific GP2 and M-Sec as molecular targets. AP-1B was revealed to connect cellular polarity and proliferation. We have also shown that AP-1B KO mice suffer from spontaneous colitis because of mis-sorting of cytokine receptors. GP2 has been shown to serve as a bacterial uptake receptor on M cells important for subsequent specific mucosal immune responses. We were also able to show that M-Sec is an important regulator for the formation of tunneling nanotubes connecting remote cells.

Research Products

• [Journal Article] AP-1B-mediated protein sorting regulates polarity and proliferation of intestinal epithelial cells in mice. (2013)
  • Author(s): Hase, K., Nakatsu, F., Ohmae, M., Sugihara, K., Shioda, N., Takahashi, D., Obata, Y., Furusawa, Y., Fujimura, Y., Yamashita, T., Fukuda, S., Okamoto, H., Asano, M., Yonemura, S., Ohno, H.
  • Journal Title: Gastroenterol. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and humoral immune responses. (2012)
  • Author(s): Ouchida, R., Mori, H., Hase, K., Takatsu, H., Kurosaki, T., Tokuhisa, T., Ohno, H., Wang, J. Y.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 109 Pages: E2699-2706
  • Peer Reviewed
• [Journal Article] Altered Ig levels and antibody responses in mice deficient for the Fc receptor for IgM (Fc□R). (2012)
  • Author(s): Honjo, K., Kubagawa, Y., Jones, D. M., Dizon, B., Zhu, Z., Ohno, H., Izui, S., Kearney, J. F., Kubagawa, H.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 109 Pages: 15882-15887
  • Peer Reviewed
• [Journal Article] AP1B plays an important role in intestinal tumorigenesis with the truncating mutation of an APC gene. (2012)
  • Author(s): Mimura, M., Masuda, A., Nishiumi, S., Kawakami, K., Fujishima, Y., Yoshie, T., Mizuno, S., Miki, I., Ohno, H., Hase, K., Minamoto, T., Azuma, T., Yoshida, M.
  • Journal Title: Int. J. Cancer Volume: 130 Pages: 1011-1020
  • Peer Reviewed
• [Journal Article] The epithelia-specific membrane trafficking factor AP-1B controls gut immune homeostasis in mice. (2011)
  • Author(s): Takahashi, D., Hase, K., Kimura, S., Nakatsu, F., Ohmae, M., Mandai, Y., Sato, T., Date, Y., Ebisawa, M., Kato, T., Obata, Y., Fukuda, S., Kawamura, Y., Dohi, T., Katsuno, T., Tokosuka, O., Waguri, S., Ohno, H.
  • Journal Title: Gatroenterol. Volume: 141 Pages: 621-632
  • Peer Reviewed
• [Journal Article] Identification of TOSO/FAIM3 as an Fc receptor for IgM. (2010)
  • Author(s): Shima, H., Takatsu, H., Fukuda, S., Ohmae, M., Hase, K., Kubagawa, H., Wang, J.-Y., Ohno, H.
  • Journal Title: Int. Immunol. Volume: 22 Pages: 149-156
  • Peer Reviewed
• [Journal Article] M-Sec promotes membrane nanotube formation by interacting with Ral and the exocyst complex. (2009)
  • Author(s): Hase, K., Kimura, S., Takatsu, H., Ohmae, M., Kawano, S., Kitamura, H., Ito, M., Watarai, H., Hazelet, C. C., Yeaman, C., Ohno, H.
  • Journal Title: Nature Cell Biol. Volume: 11 Pages: 1427-1432
  • Peer Reviewed
• [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, G. S., Fukuda, S., Ebisawa, M., Kadokura, K., Tobe, T., Fujimura, Y., Kawano, S., Nakato, G., Kimura, S., Murakami, T., Iimura, M., Hamura, K., Fukuoka, S. I., Lowe, A. W., Waguri, S., Itoh, K, Kiyono, H., Ohno, H.
  • Journal Title: Nature Volume: 462 Pages: 226-230
  • Peer Reviewed
• [Presentation] The role of M cells in intestinal immunity. (2012)
  • Author(s): Ohno, H.
  • Organizer: International Endotoxin & Innate Immunity Society Meeting 2012, Homeostatic Inflammation Symposium, Japan Endotoxin and Innate Immunity Society 2012.
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2012-10-26
• [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
  • Year and Date: 2012-10-11
• [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 Andover
  • Place of Presentation: NH, USA
  • Year and Date: 2012-06-21
• [Presentation] M cells, a unique subset of intestinal epithelial cells specialized for mucosal antigen-uptake. (2012)
  • Author(s): Ohno, H.
  • Organizer: The 2012 Spring Conference of the Korean Association of Immunologists.
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2012-04-13
• [Presentation] Function and differentiation of M cells, a unique subset of intestinal epithelial cells important for mucosal immunity. (2011)
  • Author(s): Ohno, H.
  • Organizer: ComBio2011, Plenary Lecture,
  • Place of Presentation: Cairns, Australia
  • Year and Date: 2011-09-28
• [Presentation] The role of M-Sec in tunneling nanotube formation. (2011)
  • Author(s): Ohno, H., Hase, K., Kimura, S., Fukai, S.
  • Organizer: EMBO Meeting 2011 Workshop 'Role of nanotubes in intercellular signaling'
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2011-09-10
• [Presentation] M Cells and Antigen Delivery to DCs in the Gut. (2011)
  • Author(s): Hase, K., Kawano, K., Ebisawa, M., Ohno, H.
  • Organizer: Keystone Symposia 'Dendritic Cells and the Initiation of Adaptive Immunity (J7)'
  • Place of Presentation: Santa Fe, NM, USA
  • Year and Date: 2011-02-16
• [Presentation] GP2-dependent antigen transcytosis by M cells intiates antigen-specific mucosal immune response. (2010)
  • Author(s): Hase, K., Nochi, T., Pontes, G. S., Fukuda, S., Ebisawa, M., Kadokura, K., Kiyono, H., Ohno, H.
  • Organizer: 14th International Congress of Immunology (ICI 2010)
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-26
• [Presentation] Identification of TOSO/FAIM3 as an Fc receptor for IgM. (2010)
  • Author(s): Shima, H., Takatsu, H., Fukuda, S., Ohmae, M., Hase, K., Kubagawa, H., Wang, J.-Y., Ohno, H.
  • Organizer: 14th International Congress of Immunology (ICI 2010)
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-25
• [Presentation] CCR6^<hi> CD11c^+ B cells promote M-cell differentiation in Peyer's patch. (2009)
  • Author(s): Ebisawa, M., Hase, K., Takahashi, D., Kitamura, H., Williams, I. R., Ohno, H.
  • Organizer: 第32回日本分子生物学会年会ワークショップ
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] GP2-dependent antigen transcytosis by M cells initiates antigen-specific mucosal immune response. (2009)
  • Author(s): Hase, K., Nochi, T., Pontes, G. S., Fukuda, S., Ebisawa, M., Kadokura, K., Kiyono, H., Ohno, H.
  • Organizer: 第39回日本免疫学会総会学術集会シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-02
• [Presentation] M-Sec による細胞間ナノチューブ形成促進の分子機構 (2009)
  • Author(s): 長谷耕二、高津宏之、木村俊介、大野博司
  • Organizer: 第61回日本細胞生物学会大会ワークショップ
  • Place of Presentation: 名古屋
  • Year and Date: 2009-06-03
• [Remarks]
  • URL: http://leib.rcai.riken.jp/riken/index.html