Regulatory T Cells Compensation Failure Cause the Dysregulation of Immune Response in Pristane Induced Lupus Mice Model

Introduction: Regulatory T cells' (Tregs') role remains unclear in the pathogenesis of systemic lupus erythematosus (SLE). This study was aimed at monitoring the percentage of Tregs within 32 weeks and monitoring its relationship with the percentage of other T helper (Th) cell subsets and the levels of autoantibodies and pro-inflammatory cytokines in a murine SLE model induced by pristane. Methods: Forty-eight female BALB/c mice were divided into a healthy control (HC) and a pristine-induced (PI) group. SLE was induced by a single 0.5 cc pristane intraperitoneal injection. Six from each group were sacrificed every eight weeks until 32 weeks post-pristane injection. Treg, Th1, Th2 and Th17 percentages from the spleen were measured using flowcytometry. ANA, IL-6 and IFN-alpha levels were measured from serum using ELISA. Results: The Treg percentage from the PI group increased significantly at 16 weeks compared to the HC group, while Th1, Th2 and Th17 percentages decreased. Tregs in the PI group began to reduce from the 24th to 32nd weeks, followed by an elevation of the Th1, Th2 and Th17 percentages. Tregs were negatively correlated with Th1 and Th2. Tregs in the PI group had a negative correlation with ANA and IFN-alpha levels from serum, whereas Tregs had a positive correlation with IL-6 levels. Conclusion: The compensation of Tregs observed at 16 weeks after pristane injection failed, marked by a decreasing number of Tregs, followed by an increase of Th subsets, proinflammatory cytokines and autoantibodies. This compensatory failure of Tregs could be affected by pro-inflammatory cytokines, such as IFN-alpha and IL-6.