Hyperactivation and in situ recruitment of inflammatory Vδ2 T cells contributes to disease pathogenesis in systemic lupus erythematosus.

Shanshan Yin,Wei He,Xuemei Li,Linfang Huang,Jianmin Zhang,Wenxiu Mo,Chen Zhou,Yujia Mao,Di Liang,Cai Yue,Xuan Zhang

doi:10.1038/srep14432

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.

Highlights

In this study, we measured the proportion of peripheral Vδ2 T cells as well as the status and chemokine receptor expression profiles in systemic lupus erythematosus (SLE) patients and healthy control (HC)
Our results showed that there was a significant decrease in the percentage of total γ δ T cells in the peripheral blood of new-onset SLE patients (2.61 ± 1 .79% vs. HC 8.35 ± 3.91%, p< 0.01) (Fig. 1A)
We found that the reduction in Vδ 2 T cells correlated with the severity of proteinuria and that Vδ 2 T cell infiltration into the kidneys was increased in patients with lupus nephritis, suggesting that Vδ 2 T cells are abnormally recruited to tissues to participate in tissue damage in SLE patients

Summary

Introduction

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). 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. Vδ 1 T cells have been demonstrated to express Foxp[3], and their number is substantially decreased in peripheral blood from patients with new-onset systemic lupus erythematosus (SLE)[8,9]. As Vδ 2 T cells are primarily found in the peripheral blood, we were interested in exploring whether Vδ 2 T cells can induce B cell hyperactivity to produce autoantibodies and whether Vδ 2 T cells can be recruited to local tissues to directly participate in tissue injury in SLE

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Results

Conclusion