The effect of hypoxia on regulatory T cells

• Project/Area Number: 15K21125
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology; Biological pharmacy
• Research Institution: Kyoto University (2017); Osaka University (2015-2016)
• Principal Investigator: Mikami Norihisa 京都大学, ウイルス・再生医科学研究所, 特定助教 (20710388)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 制御性T細胞 / 低酸素 / 低酸素応答 / Treg / 免疫記憶

Outline of Final Research Achievements

The present study aimed to reveal the effect of hypoxia on each Treg subset, iTreg and nTreg cells. In iTreg development, hypoxia inhibits Foxp3 expression in vitro stimulation. On the other hand, nTreg Foxp3 expression is resistant to hypoxia. Furthermore, activation markers CD103 and Tim3 are up-regulated in nTreg cells under hypoxia condition. This finding can be confirmed in vivo experiments using HIF1 cKO mice. HIF1 cKO nTreg cells show reduced level of CD103 and Tim3 expression after antigen immunization. In the settings, large number of memory B cells are observed in HIF1 cKO mice. These results demonstrate the importance of hypoxia and HIF1 in nTreg cells during immunological memory formation.