The role of human CD161+gamma delta T cells in interstitial lung disease

• Project/Area Number: 26461483
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: University of Tsukuba
• Principal Investigator: GOTO Daisuke 筑波大学, 医学医療系, 准教授 (50344891)
• Research Collaborator: SEGAWA Seiji
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 間質性肺炎 / γδT細胞 / インターフェロンγ / インターロイキン17A / IFN-γ / IL-17A / CD161 / 強皮症 / CCL-3

Outline of Final Research Achievements

I have reported the inflammatory role of γδ T cells that expressed NK1.1 in PBMCs in interstitial lung disease (ILD) mice models. In humans, mouse NK1.1 is homologous with CD161.
The proportion of CD161+γδT cells was significantly higher in systemic sclerosis (SSc) than healthy controls (HCs) and correlated negatively with serum KL-6 levels in ILD-positive SSc patients. CD161+γδT cells in ILD-positive SSc patients showed lower production of IFN-γ than in HCs. These findings suggest that CD161+γδT cells may play a regulatory role in the pathogenesis of ILD in SSc patients via IFN-γ production.
In bleomycin-induced ILD model mice, pulmonaryγδT cells were expanded and produced large amounts of IFN-γand IL-17A. Th17 cell differentiation was suppressed in the presence of IFN-γ producingγδT cells. These results suggested that pulmonaryγδT cells seem to play a regulatory role in the development of ILD via the suppression of IL-17A production.

Research Products

• [Journal Article] The regulatory role of interferon-γ producing gamma delta T cells via the suppression of T helper 17 cell activity in bleomycin-induced pulmonary fibrosis. (2016)
  • Author(s): Segawa S, Goto D, Iizuka A, Kaneko S, Yokosawa M, Kondo Y, Matsumoto I, Sumida T
  • Journal Title: Clin Exp Immunol Volume: 185 Pages: 348-360
  • DOI: 10.1111/cei.12802
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Involvement of CD161+Vδ1+γδT cells in systemic sclerosis: association with interstitial pneumonia (2014)
  • Author(s): Segawa S, Goto D, Horikoshi M, Kondo Y, Umeda N, Hagiwara S, Yokosawa M, Hirota T, Miki H, Tsuboi H, Ogishima H, Suzuki T, Matumoto I, Sumida T
  • Journal Title: Rheumatology Volume: 53 Pages: 2259-2269
  • DOI: 10.1093/rheumatology/keu246
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] サイトカイン阻害による間質性肺炎病態制御脳の検討 (2017)
  • Author(s): 瀬川誠司、後藤大輔、飯塚 晃、松本 功、住田孝之
  • Organizer: 厚生労働省「強皮症の病態解明および革新的医薬品開発の研究」研究班2016年度班会議・第20回強皮症研究会議
  • Place of Presentation: アステラス製薬（株）本社別館8階（東京都中央区）
  • Year and Date: 2017-01-14
• [Presentation] γδNKT細胞によるブレオマイシン誘導間質性肺炎病態抑制能の解析 (2016)
  • Author(s): 瀬川誠司、後藤大輔、飯塚 晃、金子駿太、横澤将宏、近藤裕也、松本 功、住田孝之
  • Organizer: 第60回日本リウマチ学会総会・学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-04-21
• [Presentation] The role of γδ T cells in bleomycin-induced pulmonary fibrosis (2015)
  • Author(s): Segawa S, Goto D, Iizuka A, Kaneko S, Yokosawa M, Kondo Y, Matsumoto I, Sumida T.
  • Organizer: The 44th Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2015-11-18
  • Int'l Joint Research
• [Presentation] The regulatory role of γδT cells in bleomycin-induced pulmonary fibrosis (2015)
  • Author(s): Segawa S, Goto D, Iizuka A, Kaneko S, Yokosawa M, Kondo Y, Matsumoto I, Sumida T.
  • Organizer: ACR 79th Annual Scientific Meeting
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2015-11-06
  • Int'l Joint Research
• [Presentation] ブレオマイシン誘導間質性肺炎におけるγδNKT細胞の機能解析 (2015)
  • Author(s): 瀬川誠司、後藤大輔、飯塚 晃、松本 功、住田孝之
  • Organizer: 第59回日本リウマチ学会総会・学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-04-23
• [Presentation] The role of TCR Vdelta1+ gammmadeltaT cells in systemic sclerosis patients with interstitial pneumonitis (2014)
  • Author(s): Segawa S, Goto D, Iizuka A, Matsumoto I, Sumida T
  • Organizer: The 43rd Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: 京都国際会議場（京都府左京区）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] 間質性肺炎合併強皮症患者におけるγδNKT細胞の機能解析 (2014)
  • Author(s): 瀬川誠司、後藤大輔、堀越正信、飯塚 晃、松本 功、住田孝之
  • Organizer: 第58回日本リウマチ学会総会・学術集会
  • Place of Presentation: グランドプリンスホテル新高輪（東京都港区）
  • Year and Date: 2014-04-24 – 2014-04-26