Study for Establishment of Novel SLE Therapy by Induction of Follicular Regulatory T Cell Differentiation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08797
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Chiba University
• Principal Investigator: SUZUKI KOTARO 千葉大学, 大学院医学研究院, 准教授 (90554634)
• Co-Investigator(Kenkyū-buntansha): 須藤 明 千葉大学, 大学院医学研究院, 准教授 (50447306) ; 岩本 太郎 千葉大学, 医学部附属病院, 助教 (80835083)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Tfr細胞 / SLE / Ascl2

Outline of Final Research Achievements

T follicular regulatory (Tfr) cells, a subset of Treg, locate to the lymphoid follicle and GC and regulate antibody responses. CD25- mature Tfr cells differentiate from CD25+ Treg cells through CD25+ immature Tfr cells. Others and we have shown that Ascl2 plays a role in Tfh cell development; however, the role of Ascl2 in the development of Tfr cells remains unclear. Here, I found that Ascl2 was highly and preferentially expressed in CD25+ Tfr cells and CD25- Tfr cells, and that the differentiation from CD25+ Tfr cells to CD25- Tfr cells was impaired by the absence of Ascl2. Furthermore, the forced Ascl2 expression in Treg cells downregulated CD25 expression and suppressed IL-2-induced phosphorylation of STAT5, which is known to suppress CD25- Tfr cell development. These results suggest that Ascl2 plays a vital role in developing Tfr cells.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本申請研究においては、FOXP3-Cre x Ascl2fl/flマウスを作成し、Tfr細胞分 化やimiquimod誘導性ループスの病態形成におけるTfr細胞内Ascl2の役割を明らかにした。本研究成果により、今後Ascl2 を標的とした Tfr細胞/Tfh細胞バランスの制御による新たなSLE治療法確立のための基盤が 構築されることが期待される。