The role of mTORC1 in dendritic cells in adaptive immune response

• Project/Area Number: 25460602
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Toho University (2014-2015); Tokyo University of Science (2013)
• Principal Investigator: OHTANI Masashi 東邦大学, 理学部, 講師 (20383713)
• Co-Investigator(Renkei-kenkyūsha): NAGAI Shigenori 東京医科歯科大学, 医歯(薬)学総合研究科, 准教授 (50348801) ; WATANABE Toshio 奈良女子大学, 大学院人間文化研究科, 教授 (60201208)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: mTOR / サイトカイン / 樹状細胞 / ｍTORC1 / mTORC1

Outline of Final Research Achievements

We have previously demonstrated that, in dendritic cells (DC), mTORC1 regulates the production of IL-12 as well as the T helper (Th) cell differentiation. In this study, we investigated the roles of mTORC1 in DC in T cell mediated-humoral immunity using DC-specific mTORC1 function-deleted (KO) mice. In KO mice, bovine serum albumin (BSA)-alum induced the production of antigen-specific IgG1 was decreased when compared with control mice. We also found the reduction of the proportion of Th2 cells in the spleen of immunized KO mice, suggesting that the mTORC1 in DC influences the antigen-specific antibody production through the regulation of Th cell differentiation.

Research Products

• [Journal Article] Loss of mTOR complex 1 induces developmental blockage in early T-lymphopoiesis and eradicates T-cell acute lymphoblastic leukemia cells. (2013)
  • Author(s): Hoshii T, Kasada A, Hatakeyama T, Ohtani M, Tadokoro Y, Naka K, Ikenoue T, Ikawa T, Kawamoto H, Fehling HJ, Araki K, Yamamura K, Matsuda S, Hirao A
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 111 Issue: 10 Pages: 3805-3810
  • DOI: 10.1073/pnas.1320265111
  • Peer Reviewed
• [Presentation] The involvement of mTORC1 in croton oil-induced cytokine expression by mouse keratinocytes. (2015)
  • Author(s): Akio Manabe, Naoko Watanabe, Masashi Ohtani
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 神戸ポートピアホテル（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] B-lineage specific loss of mTORC1 signal causes selective (2014)
  • Author(s): Ohtani M, Fujii H, Ohara O, Koyasu S, Kubo M, Matsuda S
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2014-12-10
• [Presentation] ジホモ-γ-リノレン酸産生酵母菌の経口投与による皮膚炎症応答の抑制効果 (2014)
  • Author(s): 寺津聡一郎、大谷真志、矢澤彌、植村浩、渡辺直子
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2014-11-27
• [Presentation] mTOR complex 1 is critical for B cell development but not IgA production. (2013)
  • Author(s): Ohtani, M., Fujii. H., Koyasu, S., Kubo, M., and Matsuda, S.
  • Organizer: 日本免疫学会総会・学術集会
  • Place of Presentation: 千葉
• [Presentation] Role of the mTORC1 signaling pathway in thymocyte development. (2013)
  • Author(s): Matsuda. S., and Ohtani, M.
  • Organizer: 日本免疫学会総会・学術集会
  • Place of Presentation: 千葉
• [Presentation] mTOR complex 1 regulates B cell development through IgHm expression. (2013)
  • Author(s): Ohtani, M., Watanabe, T., Hoshii, T., Koyasu, S., Ohara, O., Hirao, A., Kubo, M., and Matsuda, S.
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] mTOR complex 1 regulates B cell development. (2013)
  • Author(s): Ohtani, M., Fujii, H., Sakai, K., Hoshii, T., Watanabe, T., Koyasu, S., Hirao, A., and Matsuda, S.
  • Organizer: マクロファージ分子細胞生物学国際シンポジウム合同学術集会
  • Place of Presentation: 東京