Interleukin-21 induces T-cell activation and proinflammatory cytokine secretion in rheumatoid arthritis.

Abstract

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.

• Authors: J Li, W Shen, K Kong, Z Liu
• Journal: Scandinavian journal of immunology (Scand J Immunol) Vol. 64 Issue 5 Pg. 515-22 (Nov 2006) ISSN: 0300-9475 [Print] England
• PMID: 17032244 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Interleukins
• Receptors, Interleukin-21
• Tumor Necrosis Factor-alpha
• Interferon-gamma
• interleukin-21

Topics

• Adolescent
• Adult
• Arthritis, Rheumatoid (etiology, immunology)
• Case-Control Studies
• Cell Proliferation
• Cytokines (metabolism)
• Female
• Flow Cytometry
• Humans
• In Situ Hybridization
• Interferon-gamma (metabolism)
• Interleukins (pharmacology)
• Lymphocyte Activation
• Male
• Middle Aged
• Receptors, Interleukin-21 (blood, metabolism)
• Synovial Fluid (metabolism)
• Synovial Membrane (immunology, metabolism)
• Synovitis (immunology)
• T-Lymphocytes (physiology)
• Tumor Necrosis Factor-alpha (metabolism)