Regulation of inflammatory cytokine signaling by TRAF5

• Project/Area Number: 15H04640
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: University of Toyama (2017); Tohoku University (2015-2016)
• Principal Investigator: SO TAKANORI 富山大学, 大学院医学薬学研究部(薬学), 教授 (60294964)
• Co-Investigator(Kenkyū-buntansha): 奥山 祐子 東北大学, 医学系研究科, 助教 (50624475) ; 石井 直人 東北大学, 医学系研究科, 教授 (60291267)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000); Fiscal Year 2017: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2015: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: 炎症 / サイトカイン / TNF / 免疫 / TRAF / シグナル伝達 / 免疫学 / T細胞

Outline of Final Research Achievements

IL-17-producing helper CD4+ T cells, Th17 cells, control not only host defense against pathogens but also immune pathogenesis of inflammatory and autoimmune diseases. Th17 cells differentiate from antigen-primed naive CD4+ T cells in response to IL-6, and the IL-6-receptor signaling plays a dominant role for the development of Th17 cells. In this study, we found that TRAF2 and TRAF5 associated with the signal-transducing receptor gp130 expressed by naive CD4+ T cells differentially regulated the instructive IL-6-receptor signaling that is needed for the development of Th17 cells.

Research Products

• [Journal Article] GITR cosignal in ILC2s controls allergic lung inflammation. (2018)
  • Author(s): Nagashima H, Okuyama Y, Fujita T, Takeda T, Motomura Y, Moro K, Hidaka T, Omori K, Sakurai T, Machiyama T, Ndhlovu LC, Riccardi C, So T, Ishii N.
  • Journal Title: J Allergy Clin Immunol. Volume: - Issue: 5 Pages: 1939-1943.e8
  • DOI: 10.1016/j.jaci.2018.01.028
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] TNFR-Associated Factors 2 and 5 Differentially Regulate the Instructive IL-6 Receptor Signaling Required for Th17 Development (2016)
  • Author(s): Nagashima, H., Okuyama, Y., Hayashi, T., Ishii, N., So, T.
  • Journal Title: J Immunol Volume: 196 Issue: 10 Pages: 4082-4089
  • DOI: 10.4049/jimmunol.1501610
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mesenteric lymph nodes contribute to proinflammatory Th17-cell generation during inflammation of the samall intestine in mice. (2016)
  • Author(s): Kawabe, T., Suzuki, N., Yamaki, S., Sun, S. L., Asao, A., Okuyama, Y., So, T., Iwakura, Y., and Ishii, N.
  • Journal Title: Eur. J. Immunol. Volume: 46 Issue: 5 Pages: 1119-1131
  • DOI: 10.1002/eji.201545907
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Relationship between the magnitude of IgE production in mice and conformational stability of the house dust mite allergen, Der p 2 (2016)
  • Author(s): Hitomi Nakamura, Takatoshi Ohkuri, Takanori So, Tadashi Ueda
  • Journal Title: Biochim Biochem Acta-General Subjects Volume: 未定 Issue: 10 Pages: 2279-2284
  • DOI: 10.1016/j.bbagen.2016.04.014
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] TNFR-Associated Factors 2 and 5 Differentially Regulate the Instructive IL-6 Receptor Signaling Required for Th17 Development (2016)
  • Author(s): Hiroyuki Nagashima, Yuko Okuyama, Takaya Hayashi, Naoto Ishii, Takanori So
  • Journal Title: J. Immunol. Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] TNF Receptor-Associated Factor (TRAF) Signaling Network in CD4⁺ T-Lymphocytes (2015)
  • Author(s): Takanori So, Hiroyuki Nagashima, Naoto Ishii
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 236 Issue: 2 Pages: 139-154
  • DOI: 10.1620/tjem.236.139
  • NAID: 130005075699
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed / Open Access
• [Journal Article] TRAF5を介したシグナル伝達 (2015)
  • Author(s): 宗 孝紀、石井 直人
  • Journal Title: 分子消化器病 Volume: 12 Pages: 399-403
• [Presentation] novel regulatory role for TRAF2 and TRAF5 in the IL-6-driven Th17 development (2017)
  • Author(s): Nagashima, H., Okuyama, Y., Hayashi, T., Ishii, N., So, T.
  • Organizer: The 2017 Japan-NIH Joint Symposium on Advances in Biomedical Reserch and Disease
  • Place of Presentation: Seiryo Auditorium, Tohoku University, Sendai, Japan
  • Year and Date: 2017-02-15
  • Int'l Joint Research
• [Presentation] OX40 binding and regulation of T cell activation by the scaffolding IQGAP1 protein (2017)
  • Author(s): Okuyama, Y., Nagashima, H., Ushio-Fukai, M., Croft, M., Ishii, N., So, T.
  • Organizer: The 2017 Japan-NIH Joint Symposium on Advances in Biomedical Reserch and Disease
  • Place of Presentation: Seiryo Auditorium, Tohoku University, Sendai, Japan
  • Year and Date: 2017-02-15
  • Int'l Joint Research
• [Presentation] TNF受容体型分子 GITRによる2型自然リンパ球制御機構 (2017)
  • Author(s): 宗孝紀, 長島宏行, 藤田剛, 武田武生, 奥山祐子, 本村泰隆, 茂呂和世, 大森公貴, Ndhlovu LC, Riccardi C, 石井直人
  • Organizer: 第3回日本骨免疫学会
• [Presentation] A new regulator of OX40 co-signaling controls autoimmune neuroinflammation mediated by CD4+ T cells (2017)
  • Author(s): Okuyama Y, Nagashima H, Ushio-Fukai M, Croft M, Ishii N, So T
  • Organizer: 第46回日本免疫学会学術集会
• [Presentation] TNF receptor-associated factor 5 expressed in non-hematopoietic cells augments acute colonic damage induced by dextran sulfate sodium (2017)
  • Author(s): Phung HT, Nagashima H, Okuyama Y, Kobayashi S, Asao A, Ishii N, So T
  • Organizer: 第46回日本免疫学会学術集会
• [Presentation] Early activation of group 2 innate lymphoid cells in the lung is critically controlled by the TNFR superfamily molecule GITR (2017)
  • Author(s): So T, Nagashima H, Okuyama Y, Motomura Y, Moro K, Ndhlovu LC, Riccardi C, Ishii N
  • Organizer: 第46回日本免疫学会学術集会
• [Presentation] TRAF2 and TRAF5 binding to the signal transducing receptor gp130 inhibit JAK1 activation in the IL-6-receptor signaling complex (2017)
  • Author(s): Kimura M., Nagashima H, Ishii N, So T
  • Organizer: 第46回日本免疫学会学術集会
• [Presentation] 2 型自然リンパ球の新たな制御機構の解明 (2017)
  • Author(s): 長島宏行
  • Organizer: 第6回 Multidisciplinary meeting on atherosclerosis
  • Place of Presentation: 仙台トラストシティ（仙台市）
• [Presentation] TRAF2 and TRAF5 have redundant but unequal inhibitory roles in Th17 differentiation mediated by IL-6 (2016)
  • Author(s): Nagashima, H., Okuyama,Y., Hayashi, T., Ishii, N., So, T.
  • Organizer: 第45回日本免疫学会学術集会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾市）
  • Year and Date: 2016-12-05
• [Presentation] OX40 binding and regulation of T cell activation by the scaffolding IQGAP1 protein (2016)
  • Author(s): Okuyama, Y., Nagashima,H., Machiyama, T., Ushio-Fukai, M., Croft, M., Ishii, N., So, T.
  • Organizer: 第45回日本免疫学会学術集会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾市）
  • Year and Date: 2016-12-05
• [Presentation] TRAF adaptors limit IL-6 receptor signaling through an unexpected binding to the signaling transducer receptor gp130 (2016)
  • Author(s): So, T., Nagashima, H., Okuyama, Y., Hayashi, T., Asao, A., Kawabe, T., Yamaki, S., Nakano, H., Croft, M., Ishii, N.
  • Organizer: 16th International Congress of Immunology
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] CD4+ T cell-intrinsic TRAF5 negatively regulates Th17 cell-dependent experimental autoimmune encephalomyelitis (2016)
  • Author(s): Nagashima, H., Okuyama, Y., Hayashi, T., Asao, A., Kawabe, T., Yamaki, S., Nakano, H., Croft, M., Ishii, N., So, T.
  • Organizer: 16th International Congress of Immunology
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] TRAF2 and TRAF5 limit the differentiation of Th17 cells mediated by IL-6 (2015)
  • Author(s): Hiroyuki Nagashima, Yuko Okuyama, Takaya Hayashi, Naoto Ishii, Takanori So
  • Organizer: The 44th Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2015-11-18
• [Presentation] IQGAP1 regulates OX40 co-signaling in CD4+ T cells (2015)
  • Author(s): Yuko Okuyama, Hiroyuki Nagashima, Masuko Ushio-Fukai, Michael Croft, Naoto Ishii, Takanori So
  • Organizer: The 44th Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2015-11-18