Analysis of the mechanisms of mTORC1-mediated IL-10 regulation in antigen presenting cells and the role of mTORC1 in colitis

2012 Fiscal Year Final Research Report

• Project/Area Number: 23790546
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Kansai Medical University
• Principal Investigator: OHTANI Masashi 関西医科大学, 医学部, 助教 (20383713)
• Project Period (FY): 2011 – 2012
• Keywords: mTORC1 / 樹状細胞 / IL-10 / 腸炎

Research Abstract

mTOR complex 1 (mTORC1) affects broad aspects of cellular functions such as growth and proliferation. We have previously demonstrated that mTORC1 positively regulates IL-10 production in dendritic cells (DC). Because it has been known that IL-10 is critical for onset of colitis, we assessed the role of mTORC1 in DC in colitis using DC-specific mTORC1 function-deleted (mTORC1^DC-/-) mice. In mTORC1^DC-/-mice, IL-10 expression in intestinal DC was decreased compared with control mice. In addition, mTORC1^DC-/- mice developed more severe experimental colitis. These results indicate that mTORC1 in DC influences the onset of colitis through IL-10-mediated regulation of innate immune response in vivo.

Research Products

• [Journal Article] 樹状細胞からのIL-10産生誘導の機序 (2013)
  • Author(s): 大谷真志、松田達志
  • Journal Title: 臨床免疫・アレルギー科 Volume: 59 Pages: 325-330
• [Journal Article] Class I PI3K-mediated Akt and ERK signals play a critical role in Fc ε RI-induced degranulation in mast cells (2012)
  • Author(s): Takayama, G., Ohtani, M., Minowa, A., Matsuda, S., Koyasu S.
  • Journal Title: Int. Immunol Volume: 25 Pages: 215-220
  • DOI: DOI:10.1093/intimm/dxs105
  • Peer Reviewed
• [Journal Article] PI3K-Akt-mTORC1-S6K1/2 axis controls Th17 differentiation by regulating Gfi-1 expression and nuclear translocation of RORg (2012)
  • Author(s): Kurebayashi, Y., Nagai, S., Ikejiri, A., Ohtani, M., Ichiyama, K., Baba, Y., Yamada, T., Egami, S., Hoshii, T., Hirao, A., Matsuda, S., Koyasu, S.
  • Journal Title: Cell Reports Volume: 1 Pages: 360-373
  • DOI: DOI:10.1016/j.celrep.2012.02.007
  • Peer Reviewed
• [Journal Article] mTORC1 in intestinal CD11c^+ CD11b^+ dendritic cells regulates intestinal homeostasis by promoting IL-10 production (2012)
  • Author(s): Ohtani, M., Hoshii, T., Fujii, H., Koyasu, S., Hirao, A., Matsuda, S.
  • Journal Title: J. Immunol Volume: 188 Pages: 4736-4740
  • DOI: DOI:10.4049/jimmunol.1200069
  • Peer Reviewed
• [Presentation] mTOR complex 1 is critical for B cell development (2012)
  • Author(s): Ohatni, M., Fujii, H., Sakai, K., Hoshii, T., Watanabe, T., Koyasu, S., Hirao, A., and Matsuda, S.
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 20121211-14
• [Presentation] Role of the mTORC1 signaling pathway in acquired immunity (2012)
  • Author(s): Matsuda, S., Nagai, S., Hoshii, T., Koyasu, S., Hirao, A., and Ohtani, M.
  • Organizer: 第35回日本分子生物学会年会(ワークショップ)
  • Place of Presentation: 福岡
  • Year and Date: 20121211-14
• [Presentation] PI3K-Akt-mTORC1-S6K axis controls Th17 differentiation (2012)
  • Author(s): Nagai, S., Kurebayashi, Y., Ikejiri, A., Ohtani, M., Baba, Y., Hoshii, T., Hirao, A., Matsuda, S., and Koyasu, S.
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 20121211-14
• [Presentation] Role of the mTORC1 signaling pathway in T cell function (2012)
  • Author(s): Matsuda, S. and Ohatni, M.
  • Organizer: 第41回日本免疫学会総会・学術集会(ワークショップ)
  • Place of Presentation: 神戸
  • Year and Date: 20121205-07
• [Presentation] mTORC1 in intestinal CD11c^+CD11b^+ dendritic cells regulates intestinal homeostasis by IL-10 (2012)
  • Author(s): Ohtani M., Hoshii T., Fujii H., Koyasu S., Hirao A., and Matsuda S.
  • Organizer: 34^th Naito conference on Infection, immunity and their control for health.
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 20121016-19
• [Presentation] PI3K-Akt-mTORC1-S6K1/2経路はGfiの発現およびRORγの核移行を調節することによりTh17分化を制御する (2012)
  • Author(s): 永井重徳、紅林泰、大谷真志、松田達志、小安重夫
  • Organizer: 第22回 Kyoto T Cell Conference
  • Place of Presentation: 京都
  • Year and Date: 20120706-07
• [Presentation] 樹状細胞におけるmTORC1はIL-10産生を介して腸管免疫に関与する (2012)
  • Author(s): 大谷真志、星居孝之、平尾敦、藤猪英樹、小安重夫、松田達志
  • Organizer: 第22回 Kyoto T Cell Conference
  • Place of Presentation: 京都
  • Year and Date: 20120706-07
• [Presentation] mTORC1 in dendritic cells regulates intestinal homeostasis by IL-10 (2012)
  • Author(s): Ohtani M., Hoshii T., Fujii H., Koyasu S., Hirao A., and Matsuda S.
  • Organizer: 20^th International symposium on molecular cell biology of macrophages 2012
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 20120615-16
• [Presentation] Role of mTORC1 in immune function of dendritic cells (2011)
  • Author(s): Ohatni, M. and Matsuda, S.
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉
  • Year and Date: 20111127-29
• [Presentation] Role of the mTORC1 signaling pathway in T cell development (2011)
  • Author(s): Matsuda, S. and Ohatni, M.
  • Organizer: 第40回日本免疫学会総会・学術集会(ワークショップ)
  • Place of Presentation: 千葉
  • Year and Date: 20111127-29
• [Presentation] Role of class IA PI3K in regulatory T cell function (2011)
  • Author(s): Fujii, H., Matsuda, S., Ohtani, M., and Koyasu, S.
  • Organizer: 第40回日本免疫学会総会・学術集会(ワークショップ)
  • Place of Presentation: 千葉
  • Year and Date: 20111127-29
• [Presentation] T細胞分化過程におけるmTORC1シグナルの役割 (2011)
  • Author(s): 松田達志、大谷真志、星居孝之、平尾敦
  • Organizer: 第21回 Kyoto T Cell Conference
  • Place of Presentation: 京都
  • Year and Date: 20110603-04
• [Remarks] 関西医科大学附属生命医学研究所・生体情報部門ホームページ
  • URL: http://www3.kmu.ac.jp/bioinfo/