Altered circulating CCR6(+)and CXCR3(+) T cell subsets are associated with poor renal prognosis in MPO-ANCA-associated vasculitis

BACKGROUND: Effector memory T cells are pivotal effectors of adaptive immunity with enhanced migration characteristics and are involved in the pathogenesis of ANCA-associated vasculitis (AAV). The diversity of effector memory T cells in chemokine receptor expression has been well studied in proteinase 3 (PR3)-AAV. However, few studies have been conducted in myeloperoxidase (MPO)-AAV. Here, we characterized chemokine receptor expression on effector memory T cells from patients with active MPO-AAV. METHODS: Clinical data from newly diagnosed MPO-AAV patients and healthy subjects were collected and analyzed. Human peripheral blood mononuclear cells (PBMCs) isolated from patients with active MPO-AAV were analyzed by flow cytometry. The production of effector memory T cell-related chemokines in serum was assessed by ELISA. RESULTS: We observed decreased percentages of CD4(+) and CD8(+) T cells in the peripheral blood, accompanied by a significant decrease in CCR6-expressing T cells but an increase in CXCR3(+) T cells, in active MPO-AAV. Furthermore, the decrease in CCR6 and increase in CXCR3 expression were mainly limited to effector memory T cells. Consistent with this finding, the serum level of CCL20 was increased. In addition, a decreasing trend in the T(EM)17 cell frequency, with concomitant increases in the frequencies of CD4(+) T(EM)1 and CD4(+) T(EM)17.1 cells, was observed when T cell functional subsets were defined by chemokine receptor expression. Moreover, the proportions of peripheral CD8(+) T cells and CD4(+) T(EM) subsets were correlated with renal prognosis and inflammatory markers. CONCLUSIONS: Our data indicate that dysregulated chemokine receptor expression on CD4(+) and CD8(+) effector memory T cells and aberrant distribution of functional CD4(+) T cell subsets in patients with active MPO-AAV have critical roles related to kidney survival.