Interleukin-21 induces T-cell activation and proinflammatory cytokine secretion in rheumatoid arthritis.
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-alpha and IFN-gamma 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.
Li
J
J
Laboratory of Immunopathology, The Institute of Digestive Diseases, Department of Medicine, The Second Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
Shen
W
W
Kong
K
K
Liu
Z
Z
D000293:Adolescent; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology*; D016022:Case-Control Studies; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D053655:Receptors, Interleukin-21 / Q000097:blood / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism; D013585:Synovitis / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000098546:Interleukin-21
D016207:Cytokines; D007378:Interleukins; D053655:Receptors, Interleukin-21; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000098546:Interleukin-21