Role of CD19+CD5+CD1d+ Bregs in maintaining the Th17/Treg balance in mice with systemic lupus erythematosus complicated with atherosclerosis

Abstract

AbstractObjectiveIn this study, we aimed to investigate Bregs, their regulatory effects on Th17/Treg cell balance, and the release of downstream inflammatory factors in a mouse model of low‐density lipoprotein receptor (LDLr)−/− + Pristane.MethodsAfter the establishment of the mouse model of systemic lupus erythematosus (SLE) complicated with atherosclerosis (AS), 8‐week‐old LDLr−/− + Pristane mice (n = 10) were included in the SLE + AS group. Furthermore, 8‐week‐old MRL/lpr and C57 mice were used as the SLE and normal control groups, respectively (n = 10 per group). After feeding the mice a high‐fat diet for 14 weeks, peripheral blood and spleen of mice were collected, and Bregs, Th17, and Treg cells and related inflammatory factors were detected by flow cytometry, enzyme‐linked immunosorbent assay, and reverse‐transcription polymerase chain reaction.ResultsThe number of Bregs and Tregs in spleen lymphocytes of SLE + AS mice significantly decreased compared with the C57 group (p < .05), whereas the number of Th17 cells significantly increased (p = .000). Furthermore, the proportion of Bregs showed a negative correlation with the Th17/Treg ratio (p = .03). Mice in the SLE + AS group showed higher serum interleukin (IL)‐10, IL‐17, and tumor necrosis factor‐α levels than those in the SLE and C57 groups (p < .05). Furthermore, IL‐35 and transforming growth factor (TGF)‐β expression was reduced in the SLE + AS group compared with the C57 group (p < .05).ConclusionsThe proportion of Breg decreases was negatively associated with increased Th17/Treg which was increased in SLE + AS mice, indicating that Bregs may regulate Th17/Treg cell homeostasis and cytokine release via IL‐35 and TGF‐β production.