The distinct role of Tfh and Th17 cells and their interplay in the pathogenesis of rheumatoid arthritis

Abstract

Abstract Objectives Rheumatoid Arthritis (RA) is an autoimmune disease characterized by the presence of autoantibodies and chronic inflammation in synovium leading to joint destruction. Recently Tfh and Th17 cells have emerged as novel T cell subsets controlling autoimmunity. Our previous data showed that circulating Tfh (cTfh) and circulating Th17 (cTh17) cells were increased in RA patients. Here, we further investigated their role and interplay in the pathogenesis in RA. Design and Methods Peripheral blood was collected from 61 RA patients and 61 healthy donors. RA patients were divided into remission (<2.6) and active groups (>2.6) based on disease activity score. Clinic parameters including RF, anti-CCP, ESR and CRP were obtained. The frequencies of cTfh and cTh17 cells were measured by flow cytometry. Serum IL-21 and IL-17 were detected by ELISA. Correlations of the frequency of cTfh/IL-21 with cTh17/IL-17 and clinic parameters were statistically determined. Results The increased frequency of cTfh cells significantly correlated with the level of anti-CCP antibody (p<0.01) in active RA patients, whereas increased frequency of cTh17 cells correlated with CRP level (p<0.05). Furthermore, the level of cTfh cells and serum IL-21 level were significantly correlated with the percentage of cTh17 cells in RA patients (P<0.05). The serum IL-17 level only closely correlated with CRP in RA patients. Conclusion Tfh cells may be involved in RA pathogenesis by inducing generation of autoantibody producing plasma cells, while cTh17 cells largely related to inflammation. Tfh cells and its cytokine IL-21 may also steer T cell differentiation into Th17 cells which secrete the pro-inflammatory cytokine IL-17 and contribute to inflammation in RA.