Identification of novel therapeutic targets for rheumatoid arthritis by genome-wide analysis of gene expression in peripheral CD4 positive T cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591441
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Chiba University
• Principal Investigator: IKEDA Kei 千葉大学, 医学部附属病院, 助教 (10456014)
• Co-Investigator(Kenkyū-buntansha): NAKAJIMA Hiroshi 千葉大学, 医学部附属病院, 教授 (00322024) ; TAKATORI Hiroaki 千葉大学, 医学部附属病院, 助教 (30568225)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 関節リウマチ / IL-6 / ヘルパーT細胞 / ARID5A / Helios / Bcl-3

Outline of Final Research Achievements

We analyzed the comprehensive gene expression in peripheral CD4 positive T cells from patients with rheumatoid arthritis (RA) who achieved a good response after treatment with tocillizumab. We focused on ARID5A, Helios, and Bcl-3, the expression of which significantly decreased after treatment and further investigated the mechanisms.
We demonstrated that ARID5A is a novel molecule which inhibits Th17 differentiation probably through direct binding to RORgt. We also demonstrated that Helios potentiates the function of regulatory T cells cooperatively with FoxP3. We also demonstrated that Bcl-3 is involved in follicular helper T cell differentiation and the pathophysiology of RA.

Free Research Field

リウマチ性疾患、膠原病、臨床免疫