Hyperactivation and in situ recruitment of inflammatory Vδ2 T cells contributes to disease pathogenesis in systemic lupus erythematosus.
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ABSTRACT: In this study, we measured the proportion of peripheral Vδ2 T cells as well as the status and chemokine receptor expression profiles in SLE patients and healthy control (HC). In addition, Vδ2 T cell infiltration in the kidneys of patients with lupus nephritis was examined. The results showed that the percentage of peripheral Vδ2 T cells in new-onset SLE was decreased, and negatively correlated with the SLE Disease Activity Index score and the severity of proteinuria. These cells had a decreased apoptosis but an increased proliferation, and they showed increased accumulation in SLE kidneys. Moreover, IL-21 production and CD40L, CCR4, CCR7, CCR8, CXCR1 and CX3CR1 expression in Vδ2 T cells from SLE patients was significantly higher than from HC (p < 0.05), and these factors were downregulated in association with the repopulation of peripheral Vδ2 T cells in patients who were in remission (p < 0.05). In addition, anti-TCR Vδ2 antibodies activation significantly upregulated these chemokine receptors on Vδ2 T cells from HC, and this effect was blocked by inhibitors of PLC-γ1, MAPK/Erk, and PI3K signaling pathways. Our findings demonstrate that the distribution and function status of Vδ2 T cells from SLE patients are abnormal, and these aberrations may contribute to disease pathogenesis.
SUBMITTER: Yin S
PROVIDER: S-EPMC4585774 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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