Analysis of regulatory activity of human LAG3+ regulatory T cells

• Project/Area Number: 25860804
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: The University of Tokyo
• Principal Investigator: SUMITOMO Shuji 東京大学, 医学部附属病院, 助教 (20392996)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 制御性T細胞 / 自己免疫疾患 / IL-10 / LAG3 / 抗体産生抑制

Outline of Final Research Achievements

We identified human new regulatory T cell subset LAG3+ Treg cells. They produced high amount of IL-10 and suppressed antibody production of B cells. They also induced b cell apoptosis and suppressed in vivo inflammatory reaction in humanized mice. Our research is the first report about the detection of IL-10 producing type 1 regulatory T cells (Tr1) in human secondary lymphoid tissue. We also found that patients with rheumatoid arthritis possessed fewer LAG3+ Treg cells than healthy control. We are now investigating the mechanism of the increase in LAG3+ Treg after treatment.

Research Products

• [Journal Article] TGF-β3-expressing CD4+CD25(-)LAG3+ regulatory T cells control humoral immune responses (2015)
  • Author(s): Okamura T, Sumitomo S, Morita K, Iwasaki Y, Inoue M, Nakachi S, Komai T, Shoda H, Miyazaki J, Fujio K, Yamamoto K.
  • Journal Title: Nature Communications Volume: 6 Issue: 1 Pages: 1-14
  • DOI: 10.1038/ncomms7329
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Transcription factor early growth response 3 is associated with the TGF-β1 expression and the regulatory activity of CD4-positive T cells in vivo. (2013)
  • Author(s): Sumitomo S, Fujio K, Okamura T, Morita K, Ishigaki K, Suzukawa K, Kanaya K, Kondo K, Yamasoba T, Furukawa A, Kitahara N, Shoda H, Shibuya M, Okamoto A, Yamamoto K.
  • Journal Title: J Immunol Volume: 191 Issue: 5 Pages: 2351-9
  • DOI: 10.4049/jimmunol.1202106
  • Peer Reviewed
• [Journal Article] Egr2 and Egr3 are the unique regulators for systemic autoimmunity. (2013)
  • Author(s): Sumitomo S, Fujio K, Okamura T, Yamamoto K.
  • Journal Title: JAKSTAT Volume: 2 Issue: 2 Pages: e23952-e23952
  • DOI: 10.4161/jkst.23952
  • Peer Reviewed
• [Presentation] A quantitative alteration of Human CD4+CD25-LAG3+Tregs in patients with Rheumatoid Arthritis (2014)
  • Author(s): NAKACHI Shinichiro, SUMITOMO Shuji, TSUCHIDA Yumi, KATO Rika, TSUCHIYA Haruka, NAGAFUCHI Yasuo, HANATA Norio, KOMAI Toshihiko, SAKURAI Keiichi, SHODA Hirofumi, OKAMURA Tomohisa, FUJIO Keishi, YAMAMOTO Kazuhiko
  • 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 – 2014-12-12
• [Presentation] ヒトCD4+CD25-LAG3+制御性T細胞の機能と関節リウマチ患者における解析 (2014)
  • Author(s): 仲地 真一郎、住友 秀次、駒井 俊彦、山口 健介、花田 徳大、加藤 里佳、櫻井 恵一、土田 優美、永渕 泰雄、土屋 遥香、岡村 僚久、立石 晶子、神田 浩子、藤尾 圭志、山本 一彦
  • Organizer: 第42回日本臨床免疫学会総会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 関節リウマチ患者におけるヒトLAG3陽性T細胞の解析 (2014)
  • Author(s): 住友 秀次、仲地 真一郎、土田 優美、加藤 里佳、永渕 泰雄、駒井 俊彦、山口 健介、庄田 宏文、岡村 僚久、藤尾 圭志、山本 一彦
  • Organizer: 第35回日本炎症・再生医学会
  • Place of Presentation: 万国津梁館（沖縄県名護市）
  • Year and Date: 2014-07-01 – 2014-07-04
• [Presentation] 関節リウマチ患者におけるCD4+CD25-LAG3+制御性T細胞の解析 (2014)
  • Author(s): 仲地 真一郎、住友 秀次、土田 優美、加藤 里佳、永渕 泰雄、山口 健介、駒井 俊彦、神田 浩子、立石 晶子、藤尾 圭志、山本 一彦
  • Organizer: 第58回日本リウマチ学会学術集会
  • 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
• [Presentation] 関節リウマチ患者におけるCD4+CD25-LAG3+制御性T細胞の解析 (2014)
  • Author(s): 仲地 真一郎
  • Organizer: 第58回日本リウマチ学会学術集会
  • Place of Presentation: グランドプリンスホテル新高輪
• [Presentation] The functional analysis of human CD4+CD25-LAG3+ T cells and their association with autoimmune diseases (2013)
  • Author(s): 住友 秀次
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ