Roles of TRAF5 in the lineage commitment of helper T cell subsets

• Project/Area Number: 24590571
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Tohoku University
• Principal Investigator: SO Takanori 東北大学, 医学(系)研究科(研究院), 准教授 (60294964)
• Co-Investigator(Kenkyū-buntansha): ISHII Naoto 東北大学, 医学系研究科, 教授 (60291267)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: ヘルパーT細胞 / CD4+ T細胞 / TRAF5 / Th17 / シグナル伝達 / 自己免疫 / サイトカイン / TRAF / 免疫学 / 炎症 / T細胞

Outline of Final Research Achievements

Helper T-lymphocytes (Th cells) promotes immune-mediated inflammatory diseases, such as allergic asthma and rheumatoid arthritis. Signaling via IL-6 contributes to the development of the Th17 subset, which is one of major subpopulations of Th cells. Th17 cells activate neutrophils and are involved in autoimmune diseases. This study demonstrates that TRAF5 adaptor protein constitutively associates with a cytoplasmic region in the signaling transducing receptor for IL-6, gp130, to inhibit the IL-6 signaling and that TRAF5 works as an anti-inflammatory factor to limit immune responses mediated by pathogenic Th17 cells.

Research Products

• [Journal Article] TRAF5はIL-6シグナルを制御することでTh17分化を抑制する (2015)
  • Author(s): 宗孝紀
  • Journal Title: 臨床免疫・アレルギー科 Volume: 63 Pages: 396-400
  • NAID: 40020445095
• [Journal Article] TNF receptor-associated factor 5 limits inflammatory CD4+ T cell differentiation by antagonizing IL-6-receptor signaling. (2014)
  • Author(s): Nagashima H, Okuyama Y, Asao A, Kawabe T, Yamaki S, Nakano H, Croft M, Ishii N, and So T
  • Journal Title: Nature Immunology Volume: 15 Issue: 5 Pages: 449-456
  • DOI: 10.1038/ni.2863
  • Peer Reviewed
• [Journal Article] ヘルパーT細胞分化におけるTRAF5を介したチェックポイント制御 (2014)
  • Author(s): 宗孝紀、石井直人
  • Journal Title: 炎症と免疫 Volume: 23 Pages: 21-26
• [Journal Article] Regulation of PI-3-Kinase and Akt Signaling in T Lymphocytes and Other Cells by TNFR Family Molecules (2013)
  • Author(s): So, T. Croft, M.
  • Journal Title: Frontiers in immunology Volume: 4 Pages: 139-139
  • DOI: 10.3389/fimmu.2013.00139
  • Peer Reviewed
• [Journal Article] Regulation of the PKCtheta-NF-kB axis in T lymphocytes by the tumor necrosis factor receptor family member OX40 (2012)
  • Author(s): Takanori So, Michael Croft
  • Journal Title: Frontiers in Immunology Volume: 3 Pages: 133-133
  • DOI: 10.3389/fimmu.2012.00133
  • Peer Reviewed
• [Presentation] TRAF5によるTh17細胞分化抑制機構 (2015)
  • Author(s): 宗孝紀
  • Organizer: 第4回 Multidisciplinary meeting on atherosclerosis
  • Place of Presentation: 仙台トラストシティ カンファレンスルーム（仙台市）
  • Year and Date: 2015-01-10
• [Presentation] TRAF5 controls Th17 development by antagonizing IL-6-receptor signaling (2014)
  • Author(s): Nagashima H, Okuyama Y, Asao A, Kawabe T, Yamaki S, Nakano H, Croft M, Ishii N, and So T
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 京都国際会議場（京都市）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] OX40 and IL-7 play synergistic roles in the homeostatic proliferation of effector memory CD4+ T cells (2014)
  • Author(s): Okuyama Y, Yamaki S, Ine S, Kawabe T, Suzuki N, Nagashima H, Sun SL, So T, Sugamura K, Ishii N
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 京都国際会議場（京都市）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] TNF receptor-associated factor 5 inhibits Th17 differentiation by antagonizong IL-6-receptor signaling (2014)
  • Author(s): Nagashima H, Okuyama Y, Asao A, Kawabe T, Yamaki S, Nakano H, Croft M, Ishii N, and So T
  • Organizer: The 2nd symposium of international immunological memory and vaccine forum
  • Place of Presentation: La Jolla Institute for Allergy & Immunology, La Jolla, CA, USA
  • Year and Date: 2014-08-25 – 2014-08-26
• [Presentation] A novel molecular function of TRAF5 in CD4 T cell lineage commitment (2014)
  • Author(s): So T
  • Organizer: The 2nd symposium of international immunological memory and vaccine forum
  • Place of Presentation: La Jolla Institute for Allergy & Immunology, La Jolla, CA, USA
  • Year and Date: 2014-08-25 – 2014-08-26
• [Presentation] TRAF5はIL-6シグナルを制御することでTh17分化を抑制する (2014)
  • Author(s): 長島宏行、奥山祐子、浅尾敦子、河部剛史、山木聡史、中野裕康、Michael Croft、石井直人、宗孝紀
  • Organizer: 第68回日本細菌学会東北支部総会
  • Place of Presentation: 東北大学片平さくらホール（仙台市）
  • Year and Date: 2014-08-22 – 2014-08-23
• [Presentation] 腸管Th17細胞の産生における腸間膜リンパ節の役割 (2013)
  • Author(s): 河部剛史、孫舒嵐、鈴木信、山木聡史、浅尾敦子、宗孝紀、石井直人
  • Organizer: 第６７回日本細菌学会東北支部総会
  • Place of Presentation: 仙台市
• [Presentation] TRAF5欠損マウスでは実験的自己免疫性脳脊髄炎が増悪する (2013)
  • Author(s): 長島宏行、山木聡史、浅尾敦子、Michael Croft、石井直人、宗孝紀
  • Organizer: 第６７回日本細菌学会東北支部総会
  • Place of Presentation: 仙台市
• [Presentation] TRAF5 controls inflammatory CD4 T cells in experimental autoimmune encephalomyelitis (2013)
  • Author(s): Nagashima H, Yamaki S, Asao A, Croft M, Ishii N, So T
  • Organizer: 第４２回日本免疫学会学術集会
  • Place of Presentation: 千葉市
• [Presentation] Y chromosome-linked B and NK cell deficiency in mice (2013)
  • Author(s): Sun SL, Itoh A, Asao A, Takahashi T, So T, Kondo M, Ishii N
  • Organizer: 第４２回日本免疫学会学術集会
  • Place of Presentation: 千葉市
• [Presentation] TNF receptor-associated factor 5 によるヘルパーT細胞制御機構の解明 (2012)
  • Author(s): 長島宏行、山木聡史、Michael Croft、石井直人、宗孝紀
  • Organizer: 第６６回日本細菌学会東北支部総会
  • Place of Presentation: 東北大学 片平さくらホール
• [Presentation] TNF receptor-associated factor 5 inhibits Th17 and Tfh differentiation (2012)
  • Author(s): Hiroyuki Nagashima, Satoshi Yamaki, Michael Croft, Naoto Ishii, Takanori So
  • Organizer: 第４１回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場