Elucidation of new control mechanisms of Bob1 in Th17 cells and its application to a disease-related marker

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16614
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Ippei Ikegami 札幌医科大学, 医学部, 助教 (80837021)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: Bob1 / Th17 / EAE / Multiple Sclerosis / IL-17A

Outline of Final Research Achievements

In this study, we performed functional analysis of the transcriptional coactivator Bob1 in CD4 positive (CD4+) T cells. We found that Bob1 knock out (KO) mice were resistant to experimental autoimmune encephalomyelitis (EAE) and the number of IL-17A-producing CD4+ T cell, which is involved in the pathogenesis of EAE, was decreased Bob1 KO mice compared to that in WT mice. These results suggest that Bob1 positively regulates IL-17A production in CD4+ T cells. We revealed new mechanisms that Bob1 enhances IL-17A expression by interacting with RORγt (Biochem Biophys Res Commun. 2019). Based on these results, we generated CD4+ T cell-specific Bob1 deficient mice further to know the role of Bob1 in CD4+ T cells in vivo.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

Bob1はこれまでB細胞での機能的意義について検討されてきたが、本研究によりBob1はCD4陽性T細胞サブセットのうちTh17細胞のIL-17A産生に寄与すること見出した。Bob1は転写因子Oct1/2との結合様式が知られていたが、Th17細胞のマスター転写因子であるRORγtとBob1が結合し、転写活性を調節するという新規制御機構を初めて見出し、学術的に意義のある結果を得た。病原性CD4陽性T細胞の機能制御は不明な点が多いため、CD4陽性T細胞特異的Bob1欠損マウスを用いた研究により、CD4陽性T細胞が病態形成に寄与する疾患の理解が進み、得られた結果を医療社会に還元できると確信している。