Bregs Correction of Th17/Tregs Imbalance Regulates Systemic Lupus Erythematosus Complicated with Atherosclerosis

Abstract Objectives To investigate the dynamics of Bregs in the pathogenesis of systemic lupus erythematosus (SLE) complicating atherosclerosis in mice and their relationship with Th17 cells and Tregs. Furthermore, to determine whether spleen-derived Bregs require CD4 + T cells to correct Th17 cells/Tregs for slowing down atherosclerosis in mice with lupus. Methods A mouse model of SLE complicated with atherosclerosis (SLE + AS) was constructed and validated. The spleens of mice at weeks 1, 4, and 8 after successful modeling were collected for the detection of Bregs, Th17 cells, and Tregs by flow cytometry. In addition, 4-week-old female SCID mice were divided into the four control, intervention, sensitized, and naive groups. The control group was injected with an equal volume of saline in the tail vein, while the intervention group was injected with spleen-derived Bregs from SLE + AS mice and spleen-derived CD4 + T cells from C57 mice. The sensitized group was injected with spleen-derived Bregs from SLE + AS mice, and the naive group was injected with spleen-derived Bregs from C57 mice. After 4 weeks, the ratio of spleen and peripheral blood Bregs cells, Th17 cells, and Tregs were determined by using flow cytometry. Results The ratio of Bregs in the spleen and peripheral blood of SLE + AS mice decreased significantly over time, while the ratio of Th17 cells increased. The ratio of Tregs did not change significantly. In the intervention group, the ratio of Bregs increased, while the ratio of Th17 cells decreased. The ratio of Tregs did not change significantly. Conclusions In SLE + AS mice, Bregs decreased in the early stage and later increased. There was a persistent imbalance in the Th17 cells/Tregs ratio, indicating imbalance in the immune suppression function of Bregs. Bregs derived from the spleen of SLE + AS mice could induce differentiation and proliferation of Th17 cells and Tregs, leading to Th17 cells/Tregs imbalance in SCID mice. Normal CD4 + T cells in mice could help Bregs to exert immune function and reverse Th17 cells /Tregs imbalance.