A3.16 Specific Overexpression of Synovial Interleukin-21 + CD4 + T Cells Co-Expressing Tumour Necrosis Factor in Rheumatoid Arthritis: Role in Joint Destruction?

Background and Objectives IL-21 is a cytokine produced by activated CD4 + T cells and T follicular helper cells (TFh) that has been implicated in several autoimmune diseases. IL-21 regulates antibody production by B cells and induces osteoclastogenesis, mechanisms that contribute to rheumatoid arthritis (RA) pathology. Importantly, IL-21R blockade ameliorates arthritis in mice. Here we investigated the functional characteristics of CD4+IL-21+ T cells in RA. Materials and Methods We evaluated the expression of surface markers and cytokine production in matched peripheral blood (PB) and synovial fluid (SF) from 13 RA and 6 psoriatic arthritis (PsA) patients, and PB of 17 healthy control (HC) subjects by flow cytometry following PMA/Ionomycin stimulation ex-vivo. IL-21 concentrations were assessed by ELISA in cell-free SF samples of RA (n = 15), PsA (n = 14) and OA (n = 6) patients and in synovial biopsy culture supernatants (6 days) of RA (n = 6) and ankylosing spondylitis (AS; n = 5) patients. The effects of IL-21 were evaluated on cytokine and matrix metalloproteinase (MMP) release by RA synovial biopsies. Results The frequency of IL-21+CD4+ T cells in RA and PsA SF was significantly higher compared to PB (P Conclusions The results of this study support the notion that IL-21-producing CD4 T cells are involved in promoting synovial inflammation (TNF) and joint destruction (MMP) in RA and might be a therapeutic target in this disease.