Immune regulation through dendritic cell-specific mTOR pathway

• Project/Area Number: 22590439
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Kansai Medical University
• Principal Investigator: MATSUDA Satoshi 関西医科大学, 医学部, 准教授 (00286444)
• Co-Investigator(Renkei-kenkyūsha): OHTANI Masashi 関西医科大学, 医学部, 助教 (20383713)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: mTOR / 樹状細胞 / IL-10 / Raptor / 免疫制御 / サイトカイン

Research Abstract

Although several reports have suggested the involvement of mTORC1 in development and function of dendritic cells (DCs), its physiological roles remain obscure. By using mTORC1 signal-deficient mice lacking Raptor, an essential component of mTORC1 signal, specifically in DC lineage (referred to here as RaptorDC-/-), we found that impaired mTORC1 signal resulted in the suppression of IL-10 production in intestinal CD11c+CD11b+ DCs. We also found that RaptorDC-/- mice were highly susceptible to dextran sodium sulfate-induced colitis.

Research Products

• [Journal Article] Class I PI3K-mediated Akt and ERK signals play a critical role in FcεRI-induced degranulation in mast cells. (2013)
  • Author(s): Takayama, G., Ohtani, M., Minowa, A., Matsuda, S., and Koyasu, S.
  • Journal Title: Int. Immunol. Volume: vol.25 Issue: 4 Pages: 215-220
  • DOI: 10.1093/intimm/dxs105
  • Peer Reviewed
• [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
  • Journal Title: 臨床免疫・アレルギー科 Volume: 59 Pages: 325-330
• [Journal Article] Distinct subnuclear cyclin D3 compartments associated with proliferation and Ig variable gene repression. (2012)
  • Author(s): Powers S.E., Mandal M., Matsuda S., Miletic A.V., Gato M.H., Tanaka A., Rickert R.C., Koyasu S., Clark M.R.
  • Journal Title: J Exp Med Volume: 209 Issue: 12 Pages: 2199-2213
  • DOI: 10.1084/jem.20120800
  • 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 Issue: 10 Pages: 4736-40
  • DOI: 10.4049/jimmunol.1200069
  • Peer Reviewed
• [Journal Article] PI3K-Akt-mTORC1-S6K1/2 axis controls Th17 differentiation by regulating Gfi-1 expression and nuclear translocation of RORγ (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 Issue: 4 Pages: 360-373
  • DOI: 10.1016/j.celrep.2012.02.007
  • Peer Reviewed
• [Journal Article] mTORによる免疫制御 (2012)
  • Author(s): 松田達志
  • Journal Title: 細胞工学 Volume: 31 Pages: 1341-1346
• [Journal Article] IL-12 (2012)
  • Author(s): 松田達志
  • Journal Title: 臨床免疫・アレルギー科 Volume: 57 Pages: 86-90
• [Journal Article] Antigen-independent development of Foxp3+ regulatory T cells suppressing autoantibody production in experimental pemphigus vulgaris (2011)
  • Author(s): Yokoyama T, Matsuda S, Takae Y, Wada N, Nishikawa T, Amagai M, Koyasu S
  • Journal Title: Int Immunol Volume: 23(6) Issue: 6 Pages: 365-373
  • DOI: 10.1093/intimm/dxr020
  • Peer Reviewed
• [Journal Article] HIV-1 Nef impairs multiple T-cell functions in antigen-specific immune response in mice (2011)
  • Author(s): Fujii, H., Ato, M., Takahashi, Y., Otake, K., Hashimoto, S., Kaji, T., Tsunetsugu-Yokota, Y., Fujita, M., Adachi, A., Nakayama, T., Taniguchi, M. Koyasu, S., Takemori, T.
  • Journal Title: Int.Immunol. Volume: 23 Issue: 7 Pages: 433-441
  • DOI: 10.1093/intimm/dxr031
  • Peer Reviewed
• [Presentation] mTOR complex1 is critical for B cell development. (2012)
  • Author(s): Ohtani, 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: 2012-12-14
• [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
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-13
• [Presentation] Role of the mTORC1 signaling pathway in T cell function. (2012)
  • Author(s): Matsuda, S., and Ohtani, M.
  • Organizer: 第41回日本免疫学会総会・学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-05
• [Presentation] Role of the mTORC1 signaling pathway in acquired immunity. (2012)
  • Author(s): Matsuda, S. et al.
  • Organizer: 第３５回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場、マリンメッセ福岡（福岡県）
  • Invited
• [Presentation] mTOR complex 1 is critical for B cell development. (2012)
  • Author(s): Ohtani, M. et al.
  • Organizer: 第３５回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場、マリンメッセ福岡（福岡県）
• [Presentation] PI3K-Akt-mTORC1-S6K axis controls Th17 differentiation. (2012)
  • Author(s): Nagai, S. et al.
  • Organizer: 第３５回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場、マリンメッセ福岡（福岡県）
• [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
  • Place of Presentation: 神戸国際会議場（兵庫県）
• [Presentation] 制御性T細胞機能発現におけるPI3Kの役割 (2012)
  • Author(s): 藤猪英樹 他
  • Organizer: 第22回Kyoto T Cell Conference
  • Place of Presentation: 和順会館（京都府）
• [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 他
  • Organizer: 第22回Kyoto T Cell Conference
  • Place of Presentation: 和順会館（京都府）
• [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 他
  • Organizer: 第22回Kyoto T Cell Conference
  • Place of Presentation: 和順会館（京都府）
• [Presentation] mTORC1 in dendritic cells regulates intestinal homeostasis by IL-10. (2012)
  • Author(s): Ohtani, M. et al.
  • Organizer: 20th International Symposium on Molecular Cell Biology of Macrophages 2012
  • Place of Presentation: 東京大学（東京都）
• [Presentation] Forced expression of a constitutively active form of p110δ results in decrease of double positive thymocytes during thymocyte development (2011)
  • Author(s): Yamana, A., et al
  • Organizer: 第34回分子生物学会総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-12-14
• [Presentation] Role of the mTORC1 signaling pathway in T cell development. (2011)
  • Author(s): Matsuda, S. and Ohatni, M.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
  • Year and Date: 2011-11-29
• [Presentation] Role of mTORC1 in immune function of dendritic cells. (2011)
  • Author(s): Ohatni, M. and Matsuda, S.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
  • Year and Date: 2011-11-29
• [Presentation] Role of the mTORC1 signaling pathway in T cell development (2011)
  • Author(s): Matsuda, S., Ohatni, M.
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉県)
  • Year and Date: 2011-11-29
• [Presentation] Role of mTORC1 in immune function of dendritic cells (2011)
  • Author(s): Ohatni, M., Matsuda, S.
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉県)
  • Year and Date: 2011-11-29
• [Presentation] Role of class IA PI3K in regulatory T cell function (2011)
  • Author(s): Fujii, H., et al
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉県)
  • Year and Date: 2011-11-29
• [Presentation] PI3K-Akt-mTORC1 axis controls Th17 differentiation by regulation of Gfi-1 and RORγt. (2011)
  • Author(s): Nagai, S., Kurebayashi, Y., Baba, Y.,Matsuda, S., and Koyasu, S.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張
  • Year and Date: 2011-11-28
• [Presentation] PI3K-Akt-mTORC1 axis controls Th17 differentiation by regulation of Gfi-1 and RORγt (2011)
  • Author(s): Nagai, S., et al
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉県)
  • Year and Date: 2011-11-28
• [Presentation] Analysis of the molecular mechanism of the mTOR-mediated IL-10 expression in dendritic cells (2010)
  • Author(s): 大谷真志
  • Organizer: 第14回国際免疫学会
  • Place of Presentation: 神戸国際展示場(神戸)
  • Year and Date: 2010-08-24
• [Presentation] Cre依存的にAML1の発現が誘導できるAML1-TGマウスをCD4-Cre-TGマウスと交配させた際に生じる目の異常の発見 (2010)
  • Author(s): 渡邊利雄
  • Organizer: 第20回Kyoto T Cell Conference
  • Place of Presentation: 芝蘭会館(京都)
  • Year and Date: 2010-06-05
• [Remarks]
  • URL: http://www3.kmu.ac.jp/bioinfo/
• [Remarks] 関西医科大学付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/index.html
• [Remarks]
  • URL: http://www3.kmu.ac.jp/bioinfo/
• [Remarks]
  • URL: http://www3.kmu.ac.jp/bioinfo/