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

Autor: Zhonghua Liao, Jiale Tang, Liying Luo, Shuanglinzi Deng, Lisa Luo, Fangyuan Wang, Xiangning Yuan, Xinyue Hu, Juntao Feng, Xiaozhao Li
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Arthritis Research & Therapy, Vol 23, Iss 1, Pp 1-11 (2021)
Druh dokumentu: article
ISSN: 1478-6362
DOI: 10.1186/s13075-021-02576-x
Popis: Abstract 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 TEM17 cell frequency, with concomitant increases in the frequencies of CD4+ TEM1 and CD4+ TEM17.1 cells, was observed when T cell functional subsets were defined by chemokine receptor expression. Moreover, the proportions of peripheral CD8+ T cells and CD4+ TEM 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.
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