VEGFD/VEGFR2 axis induces the dedifferentiation of high endothelial venules and impairs lymphocyte homing.

OBJECTIVE: Membranous nephropathy is a leading cause of adult-onset nephrotic syndrome. Peripheral T cells and myeloid-derived suppressor cells (MDSCs) are closely associated with autoimmune diseases, while their exact roles and interaction in these processes are unclear. Here, we studied the roles of T cells, MDSCs, and their subsets in patients with idiopathic membranous nephropathy (IMN).

MATERIALS AND METHODS: 35 IMN patients and 30 healthy controls were included in this retrospective study. Flow cytometry was performed to determine the phenotype of human T cells and MDSCs in peripheral blood mononuclear cells (PBMCs). Anti-PLA2R was measured by ELISA. Values ≥ 20 RU/mL were defined as positive and < 14 RU/mL as negative.

RESULTS: A higher ratio of CD4/CD8 T cells with a lower proportion of Tregs, a remarkably lower proportion of G-MDSCs (but not M-MDSCs), lower frequency of PD-L2+G-MDSCs, and higher frequency of PD-L1+M-MDSCs were found in IMN patients compared to healthy controls. The ratio of CD4/CD8 T cells was higher, and the frequencies of PD-1+CD4+ T cells, CTLA-4+CD4+ T cells, PD-1+Tregs, and CTLA-4+Tregs were lower in PBMCs of PLA2R-positive IMN patients compared to PLA2R-negative IMN patients.

CONCLUSION: Tregs and G-MDSCs were reduced in the circulation of the IMN patients, which may promote understanding of the crucial functions that are mediated by these cells in the pathogenesis of IMN.