Regulatory T Cells Accelerate the Repair Process of Renal Fibrosis by Regulating Mononuclear Macrophages

Abstract

Background: We aimed to investigate the mechanisms of renal fibrosis and explore the effect of CD4+CD25+Foxp3+ regulatory T cells (Treg) on renal fibrosis after the obstruction was removed.

Methods: Fifty-five C57BL/6 mice were randomly divided into three groups: the unilateral ureteral obstruction (UUO) group, the relief for unilateral ureteral obstruction (RUUO) group, and the RUUO+Treg group. Renal fibrosis indexes of RUUO mice were evaluated using hematoxylin and eosin (HE) and, Masson staining and immunohistochemistry after CD4+CD25+Treg cells were injected into the tail vein at the moment of recanalization. We detected the levels of Treg, M1, and M2 markers by flow cytometry, and the levels of transforming growth factor (TGF)-β1, interleukin (IL)-1β, IL-6 and IL-10 using ELISA.

Results: The tubular necrosis score, AO value of α-SMA (smooth muscle actin), and collagen area on the 3rd and 14th days post RUUO were up-regulated compared with the 7th day post RUUO (P<0.05). After injection of Treg via tail vein, the tubular necrosis score, AO value of α-SMA, TGF-β1 level, and collagen area in the RUUO+Treg group on the 14th day were down-regulated compared with the RUUO group (P<0.05). Moreover, Treg could transform M1 macrophages into M2 macrophages, manifesting as up-regulated expression of CD206 compared with the RUUO group (P<0.05). Treg could also down-regulate the secretion of IL-6 and IL-1β while up-regulating the secretion of IL-10 in vitro compared with the M1 group (P<0.05).

Conclusions: The kidney could deteriorate into a state of injury and fibrosis after the obstruction was removed, and Treg could effectively protect the kidney function.

Keywords: Macrophages; Mouse model; Obstructive nephropathy; Regulatory T cells; Renal fibrosis.