Regulation of T cell functions by the transcription factor JunB

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07516
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Toho University
• Principal Investigator: Yamazaki Soh 東邦大学, 医学部, 准教授 (70315084)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: AP-1 / 転写因子 / JunB / 制御性T細胞 / ヘルパーT細胞 / 大腸炎

Outline of Final Research Achievements

Regulatory T cells (Treg cells) are known to play important roles in preventing excess immune reactions, how Treg cells are generated in vivo has not been fully elucidated. We revealed that Treg cells are not efficiently developed in mice deficient in the transcription factor JunB due to impairment in activation of IL-2 signaling. We also found that dextran sulfate sodium (DSS)-induced colitis, a mouse model for human ulcerative colitis, was exacerbated in JunB-deficient mice because of the reduction in the Treg cell number. Injection of a high dose of IL-2 into JunB-deficient mice resulted in mitigation of the colitis by expansion of Treg cells.

Free Research Field

免疫学（腸管免疫、炎症制御）、分子生物学（遺伝子発現調節）

Academic Significance and Societal Importance of the Research Achievements

潰瘍性大腸炎などの炎症性疾患や多くの自己免疫疾患は、治療戦略はもとより、発症・増悪メカニズムについても詳細が明らかでない。本研究により、転写因子JunBがIL-2シグナルの活性化を通じてTreg細胞の誘導に関与し、大腸炎モデルを抑制することが明らかになったので、JunBのはたらきやIL-2シグナルの強度を調節するというアプローチにより、Treg細胞を介して症状を緩和するという新しい治療法の可能性が示された。