Regulation of GM-CSF-producing Th cells

• Project/Area Number: 26670477
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kyoto University (2015-2016); Osaka University (2014)
• Principal Investigator: Hirota Keiji 京都大学, ウイルス・再生医科学研究所, 准教授 (90631250)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: サイトカイン / ヘルパーT細胞 / GM-CSF / 自己免疫疾患

Outline of Final Research Achievements

In this study, we identified TNFRSF18 as a specific surface molecule for the regulation of GM-CSF by activated Th cells in vitro. The activation of TNFRSF18 signaling also induced GM-CSF production from effector/memory Th cells in vivo, indicating that this signal cascade is a key molecular pathway to specifically enhance production of GM-CSF. Furthermore, TNFSF18-deficient mice were resistant to the development of experimental autoimmune encephalomyelitis, accompanying impaired production of GM-CSF by tissue infiltrating pathogenic Th cells. Thus, targeting this molecular pathway may be useful for a therapeutic means to prevent or treat the autoimmune disease.

Research Products

• [Journal Article] Dysbiosis contributes to arthritis development via activation of autoreactive T cells in the intestine. (2016)
  • Author(s): Maeda Y, Kurakawa T, Umemoto E, Motooka D, Ito Y, Gotoh K, Hirota K, Matsushita M, Furuta Y, Narazaki M, Sakaguchi N, Kayama H, Nakamura S, Iida T, Saeki Y, Kumanogoh A, Sakaguchi S, and Takeda K
  • Journal Title: Arthritis Rheum Volume: 68 Issue: 11 Pages: 2646-2661
  • DOI: 10.1002/art.39783
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 「自己免疫性関節炎を惹起するヘルパーTサブセットと認識自己抗原」：慢性炎症性疾患の新たな展開 (2016)
  • Author(s): 廣田 圭司
  • Journal Title: 最新医学 Volume: 71 Pages: 2320-2325
• [Journal Article] 関節リウマチの病態形成に関与するT細胞クローンの同定と新規自己抗原RPL23A (2015)
  • Author(s): 廣田圭司、橋本求、坂口志文
  • Journal Title: 感染・炎症・免疫 Volume: 45 Pages: 67-70
• [Journal Article] Th17細胞の機能制御と自己免疫疾患 (2015)
  • Author(s): 廣田圭司
  • Journal Title: 実験医学 増刊 Volume: 33 Pages: 1877-1881
• [Journal Article] Detection of T-cell responses to a ubiquitous cellular protein in autoimmune disease. (2014)
  • Author(s): Ito Y, Hashimoto M, Hirota K, Ohkura N, Morikawa H, Nishikawa H, Tanaka A, Furu M, Ito H, Fujii T, Nomura T, Yamazaki S, Morita A, Vignali D, Kappler J, Matsuda S, Mimori T, Sakaguchi N, Sakaguchi S.
  • Journal Title: Science Volume: 346 Issue: 6207 Pages: 363-8
  • DOI: 10.1126/science.1259077
  • Peer Reviewed
• [Journal Article] Activation of the Aryl Hydrocarbon Receptor Dampens the Severity of Inflammatory Skin Conditions. (2014)
  • Author(s): 2)Di Meglio P, Duarte JH, Ahlfors H, Owens ND, Li Y, Villanova F, Tosi I, Hirota K, Nestle FO, Mrowietz U, Gilchrist MJ, Stockinger B.
  • Journal Title: Immunity Volume: 40 Issue: 6 Pages: 989-1001
  • DOI: 10.1016/j.immuni.2014.04.019
  • Peer Reviewed
• [Presentation] An inflammatory cellular network of autoimmune Th17 cells, GM-CSF-producing ILCs and synoviocytes in the development of autoimmune arthritis (2017)
  • Author(s): Keiji Hirota
  • Organizer: Keystone symposia, Immune Regulation in Autoimmunity and Cancer
  • Place of Presentation: Whistler, Canada
  • Year and Date: 2017-03-26
  • Int'l Joint Research
• [Presentation] Inflammatory circuit of Th17 cells, GM-CSF-producing fibroblast-like synoviocytes, and ILCs in the development of autoimmune arthritis (2016)
  • Author(s): Keiji Hirota
  • Organizer: 第16回 国際免疫学会
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] Th17 cells orchestrate an inflammatory circuit in the development of autoimmune arthritis (2016)
  • Author(s): Keiji Hirota
  • Organizer: World Immune Regulation Meeting X
  • Place of Presentation: Davos, Switzerland
  • Year and Date: 2016-03-16
  • Int'l Joint Research / Invited
• [Presentation] Generation of highly self-reactive T helper cells in SKG autoimmune arthritis (2015)
  • Author(s): Keiji Hirota
  • Organizer: 第１０回 研究所ネットワーク国際シンポジウム
  • Place of Presentation: 北海道
  • Year and Date: 2015-07-23
  • Int'l Joint Research / Invited
• [Presentation] T cell-dependent IgA responses by plastic Th17 cells (2014)
  • Author(s): Keiji Hirota
  • Organizer: The American Association of Immunologists Annual Meeeting.
  • Place of Presentation: Pittsburgh, Pennsylvania, USA.
  • Year and Date: 2014-05-02 – 2014-05-06
  • Invited