Interleukin (IL)‐21 is a CD4+ T‐cell‐derived cytokine, which is involved in innate and adaptive immune response. In this study, we analysed IL‐21 receptor (IL‐21R) expression in peripheral blood and synovial fluid mononuclear cells, and investigated the role of IL‐21 in the induction of proinflammatory cytokine production by peripheral blood T cells (PB‐T) and synovial fluid T cells (SF‐T) from patients with rheumatoid arthritis (RA). Immunohistochemical staining demonstrated that IL‐21R‐positive cells were significantly increased in inflamed synovial tissues of RA patients compared with osteoarthritis (OA) and healthy controls. Flow cytometric analysis confirmed that IL‐21R was mainly expressed in freshly isolated CD4, CD8, B and NK cells from peripheral blood and synovial fluid, but decreased gradually in T cells 24 h after anti‐CD3 stimulation. PB‐ and SF‐T cells from RA patients were more responsive to IL‐21 when compared with controls. Importantly, isolated PB‐ or SF‐T cells from RA patients, when stimulated with IL‐21 and anti‐CD3 MoAb, secreted markedly higher levels of TNF‐α and IFN‐γ than controls. These data indicate that IL‐21R is overexpressed in the inflamed synovial membrane and in peripheral blood or synovial fluid leukocytes of RA patients, and that IL‐21 enhances local T‐cell activation, proliferation and proinflammatory cytokine secretion. Thus, blockade of IL‐21R signalling pathway may have a therapeutic potential in acute RA patients.

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