Chemotaxis of V{delta}2 T cells to the joints contributes to the pathogenesis of rheumatoid arthritis
To explore the role of V2 T cells in the pathogenesis of rheumatoid arthritis (RA).
Sixty-eight patients with RA, 21 patients with osteoarthritis and 21 healthy controls were enrolled in the study. All patients with RA fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism criteria for RA. Peripheral V2T population, chemokine receptor expression and proinflammatory cytokine secretion were quantified by flow cytometry. The infiltration of V2 T cells within the synovium was examined by immunohistochemistry and flow cytometry. The effect of tumour necrosis factor (TNF)-α and interleukin (IL)-6 on V2 T migration was determined by flow cytometry and transwell migration assay.
Peripheral V2T cells, but not V1 T cells, were significantly lower in patients with RA, which was negatively correlated with disease activity gauged by Disease Activity Score in 28 joints. V2 T cells from RA accumulated in the synovium and produced high levels of proinflammatory cytokines including interferon- and IL-17. Phenotypically, V2 T cells from RA showed elevated chemotaxis potential and expressed high levels of chemokine receptors CCR5 and CXCR3, which was driven by increased serum TNF-α through nuclear factor kappa B signalling. In vivo, TNF-α neutralising therapy dramatically downregulated CCR5 and CXCR3 on V2 T cells and repopulated the peripheral V2 T cells in patients with RA.
High levels of TNF-α promoted CCR5 and CXCR3 expression in V2 T cells from RA, which potentially infiltrated into the synovium and played crucial roles in the pathogenesis of RA. Targeting V2 T cells might be a potential approach for RA.
Publisher URL: http://ard.bmj.com/cgi/content/short/76/12/2075
DOI: 10.1136/annrheumdis-2016-211069
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