Roles of BCL-3 in the development of TFH cells and the pathogenesis of rheumatoid arthritis

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461460
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Chiba University
• Principal Investigator: SUZUKI Kotaro 千葉大学, 医学部附属病院, 講師 (90554634)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 関節リウマチ / Bcl-3 / Bcl-6 / 濾胞ヘルパーT細胞

Outline of Final Research Achievements

We have previously shown that expression of the Bcl-3 gene is down-regulated in CD4+ T cells from patients with rheumatoid arthritis (RA) following tocilizumab therapy. The objective of this study was to examine the role of Bcl-3 in the pathogenesis of RA. We examined the roles of IL-6 signaling in the induction of Bcl-3. We analyzed the gene expression profiles of Bcl-3-transduced CD4+ T cells by RNA sequencing. The effects of enforced expression of Bcl-3 on the development of follicular helper T (Tfh) cells were evaluated. IL-6 induced Bcl-3 expression in CD4+ T cells in a STAT3-dependent manner. Transcriptome analysis revealed that the expression of Bcl-6, a master regulator of Tfh cell differentiation, was significantly up-regulated by the enforced Bcl-3 expression. The enforced Bcl-3 expression increased the numbers of IL-21-producing Tfh-like cells. Bcl-3 is involved in the development of Tfh cells and the pathogenesis of RA, presumably by inducing IL-21 production.

Free Research Field

リウマチ学