Deficiency of ?-arrestin1 ameliorates collagen-induced arthritis with impaired TH17 cell differentiation.

ABSTRACT: Rheumatoid arthritis (RA) is an inflammatory disease in which interleukin 17 (IL-17)-producing T helper 17 (T(H)17) cells have been critically involved. We show that in patients with RA, the expression of a multifunctional regulator ?-arrestin1 was significantly up-regulated in peripheral and synovial CD4(+) T cells, which correlated well with active phases of RA. In collagen-induced arthritis, deficiency of ?-arrestin1 ameliorated disease with decreased T(H)17 cell differentiation, proinflammatory cytokine production, synovitis, and cartilage and bone destruction. Further mechanistic study reveals that ?-arrestin1 promoted signal transducer and activator of transcription 3 (STAT3) activation required for T(H)17 cell differentiation through scaffolding the interaction of Janus kinase 1 and STAT3. These findings indicate a critical role for ?-arrestin1 in the pathogenesis of collagen-induced arthritis and T(H)17 cell differentiation and suggest ?-arrestin1 as a potential diagnostic biomarker and therapeutic target for RA.

SUBMITTER: Li J 

PROVIDER: S-EPMC3645576 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature