Celastrol Ameliorated Lupus in Fas-Deficiency MRL/lpr Mice via Regulating in Vivo Immune Response of Lymphocytes

Abstract Background Celastrol is the bioactive constituent extracted from tripterygium wilfordii (Thunder God Vine). In present study, we explore whether celastrol would exhibit a regulatory effect on adaptive immune response in vivo in MRL/lpr mice. Methods In present study, we combined following approaches to determine the underlying mechanism of celastrol treatment on MRL/lpr mice, including Elisa, Luminex, and flow cytometry. Results Celastrol treatment significantly prevented enlargement of spleen and lymph node, alleviated renal injuries, and reduced production of ANA and anti-dsDNA antibody. Celastrol treatment also strikingly decreased serum levels of multiple cytokines and antibody subsets in MRL/lpr mice. Celastrol treatment also reduced Th1 and TNF producing cells frequencies in CD4 + T cells of MRL/lpr mice. Celastrol treatment strikingly prevented CD138 + T cells accumulation and increased apoptosis level of CD138 + T cells in MRL/lpr mice. In addition, celastrol treatment prevented plasma cells formation from B cells in MRL/lpr mice by decreasing activated and germinal center B cells frequency in B cells. Conclusions Celastrol treatment has a significantly therapeutic effect on MRL/lpr mice. Both alleviated accumulation of CD138 + T cells and reduced formation of plasma cells in MRL/lpr mice induced by celastrol treatment together contributed to the reduced secretion of autoantibody in celastrol-treated MRL/lpr mice.