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Chemotaxis of Vδ2 T cells to the joints contributes to the pathogenesis of rheumatoid arthritis.
- Source :
- Annals of the Rheumatic Diseases; Dec2017, Vol. 76 Issue 12, p2075-2084, 10p, 6 Graphs
- Publication Year :
- 2017
-
Abstract
- <bold>Objectives: </bold>To explore the role of Vδ2 T cells in the pathogenesis of rheumatoid arthritis (RA).<bold>Methods: </bold>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 Vδ2T population, chemokine receptor expression and proinflammatory cytokine secretion were quantified by flow cytometry. The infiltration of Vδ2 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 Vδ2 T migration was determined by flow cytometry and transwell migration assay.<bold>Results: </bold>Peripheral Vδ2T cells, but not Vδ1 T cells, were significantly lower in patients with RA, which was negatively correlated with disease activity gauged by Disease Activity Score in 28 joints. Vδ2 T cells from RA accumulated in the synovium and produced high levels of proinflammatory cytokines including interferon-γ and IL-17. Phenotypically, Vδ2 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 Vδ2 T cells and repopulated the peripheral Vδ2 T cells in patients with RA.<bold>Conclusions: </bold>High levels of TNF-α promoted CCR5 and CXCR3 expression in Vδ2 T cells from RA, which potentially infiltrated into the synovium and played crucial roles in the pathogenesis of RA. Targeting Vδ2 T cells might be a potential approach for RA. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00034967
- Volume :
- 76
- Issue :
- 12
- Database :
- Complementary Index
- Journal :
- Annals of the Rheumatic Diseases
- Publication Type :
- Academic Journal
- Accession number :
- 126382838
- Full Text :
- https://doi.org/10.1136/annrheumdis-2016-211069