Analysis of CD2-mediated gene regulatory mechanisms about function and survival in regulatory T cells

• Project/Area Number: 26860336
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Dokkyo Medical University
• Principal Investigator: Kashiwakura Yuji 獨協医科大学, 医学部, 助教 (40382890)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 制御性T細胞 / CD2 / CD２ / 遺伝子発現

Outline of Final Research Achievements

We focused on the role of CD2 in regulatory T (Treg) cells. We examined whether the CD2 signaling solely affects the function and induction of Treg cells. CD48-Fc, which is composed of extra-cellular portion of murine CD48 and murine Fcγ, was used for CD2-stimulation. We found that CD2-stimuli up-regulated Foxp3 expression and maintained the regulatory functions in Treg cells. CD2-induced Foxp3 up-regulation was partially dependent on IL-2. It was found that CD2- and TCR-stimuli synergistically increased the Foxp3 expression in Treg cells. But, CD2-stimuli decrease Bim expression as compared with TCR-stimuli, supporting survival Treg cells. Furthermore, we found that CD2-stimuli induced Foxp3 expression in naive T cells in the presence of TGF-β. It was confirmed that PI3K/AKT and JAK/STAT signals were involved in CD2-induced Foxp3 expression in naive T cells. Importantly, the CD2-induced Treg cells exerted regulatory effects on CD8+ T cell activation.

Research Products

• [Journal Article] Peyer's patch innate lymphoid cells regulate commensal bacteria expansion (2016)
  • Author(s): Hashiguchi, M., Kobayashi, A., Kashiwakura, Y., Kojima, H., Kanno, Y., Kobata, T.
  • Journal Title: Eur. J. Immunol. (Suppl. 1) Volume: 46 Pages: 145-145
• [Journal Article] Glucose and fatty acids in T cell-metabolism and their roles in immune regulation (2016)
  • Author(s): Kojima, H., Kashiwakura, Y., Kanno, Y., Hashiguchi, M., Kobata, T.
  • Journal Title: Eur. J. Immunol. (Suppl. 1) Volume: 46 Pages: 444-444
• [Journal Article] Foxp3+ regulatory T cells are maintained and induced by CD2-stimulation ex vivo (2016)
  • Author(s): Kashiwakura, Y., Kanno, Y., Hashiguchi, M., Kobata, T., Kojima, H.
  • Journal Title: Eur. J. Immunol. (Suppl. 1) Volume: 46 Pages: 749-750
• [Presentation] ヘパリンによる制御性T細胞誘導効果の解析 (2017)
  • Author(s): 柏倉裕志, 菅野裕美子, 橋口昌章, 小端哲二, 小嶋英史
  • Organizer: 第39回 日本血栓止血学会学術集会
  • Place of Presentation: 名古屋国際会議場 愛知県名古屋市
  • Year and Date: 2017-06-08
• [Presentation] Anticoagulant heparin enhances the induction of regulatory T cells and regulates the immune responses (2016)
  • Author(s): Yuji Kashiwakura, Masaaki Hashiguchi, Yumiko Kanno, Tetsuji Kobata, and Hidefumi Kojima
  • 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] Foxp3+ regulatory T cells are maintained and induced by CD2-stimulation ex vivo (2016)
  • Author(s): Y Kashiwakura, Y Kannno, M Hashiguchi, T Kobata, and H Kojima
  • Organizer: International Congress of Immunology 2016
  • Place of Presentation: Melbourne Convention and Exhibition Centre, Melbourne, Australia
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] Foxp3+ regulatory T cells are maintained and induced by CD2-stimulation ex vivo (2016)
  • Author(s): Yuji Kashiwakura, Yumiko Kanno, Masaaki Hashiguchi, Tetsuji Kobata, and Hidefumi Kojima.
  • Organizer: 16th International Congress of Immunology
  • Place of Presentation: Melbourne Convention and Exhibition Centre
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] CD2-stimulation induces Foxp3 in both CD4+CD25+ regulatory T cells and CD4+CD25- naive T cells in cooperation with TGF-β (2015)
  • Author(s): Kashiwakura Yuji, Hashiguchi Masaaki, Kanno Yumiko, Kobata Tetsuji and Hidefumi Kojima.
  • Organizer: 第44回日本免疫学会総会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2015-11-18
• [Presentation] CD2 stimulation upregulates Foxp3 in murine peripheral regulatory T cells. (2014)
  • Author(s): Kashiwakura Yuji, Hashiguchi Masaaki, Kanno Yumiko, Kobata Tetsuji and Hidefumi Kojima.
  • Organizer: 第43回日本免疫学会総会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2014-12-10 – 2014-12-12