PRO-INFLAMMATORY FUNCTIONS OF BHLHE40 AND DUSP6 IN RHEUMATOID ARTHRITIS

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the synovium. This thesis aims to investigate RA pathogenesis by focusing on CD4+ T cell function, particularly T cell-derived inflammatory cytokines, using a well-established murine arthritis model. Firstly, it was fond that the expression of BHLHE40 to be a downstream factor of STAT5 in a novel T helper cell subset, THGM. Moreover, BHLHE40 was required for the differentiation of THGM cells and their pathogenic roles in antigen induced arthritis (AIA) in mouse. Secondly, we investigated the pathogenic role of dual-specific phosphatase 6 (DUSP6) in inflammation and rheumatoid arthritis. DUSP6 can promote the pathogenesis of rheumatoid arthritis but inhibiting the phosphorylation of MAPK, STAT3, AKT and FoxO1. Here, we found that DUSP6 regulates inflammation and arthritis in a MAPK-independent manner.