Celastrol Ameliorates Lupus by Promoting Apoptosis of Autoimmune T Cells and Preventing Autoimmune Response in MRL/lpr Mice

Abstract

Abstract Celastrol is a bioactive constituent extracted from tripterygium wilfordii (Thunder God Vine). In the present study, we investigated whether Celastrol could have a regulatory effect on the autoimmune response in MRL/lpr mice. Our results demonstrated that Celastrol had a therapeutic effect on MRL/lpr mice by preventing the enlargement of the spleen and lymph nodes, alleviating renal injury, and reducing the levels of ANA and anti-dsDNA antibodies. Furthermore, Celastrol suppressed the in vivo inflammatory response in MRL/lpr mice by dramatically reducing the serum levels of multiple cytokines and production of antibody subsets. In addition, Celastrol treatment reduced in vitro anti-CD3 antibody stimulation-induced the number of Th1 and TNF-producing cells in CD4 + T cells of MRL/lpr mice. Celastrol treatment significantly affected B cell differentiation and prevented the generation of plasma cells from B cells in MRL/lpr mice by decreasing the number of activated and germinal center B cells. This contributed to the reduced secretion of autoantibodies in Celastrol-treated MRL/lpr mice. Celastrol treatment also affected T-cell differentiation and significantly reduced Tcm cell frequencies in MRL/lpr mice. Importantly, Celastrol treatment markedly and specifically promoted apoptosis of CD138 + T cells and suppressed autoimmune T-cell accumulation in MRL/lpr mice. The reduced number of CD138 + T cells further affected B-cell differentiation and subsequently resulted in the reduced number of autoreactive plasma cells which led to the reduced secretion of autoantibodies. Our results indicated that Celastrol had therapeutic effects on lupus by specifically promoting apoptosis of autoimmune T cells.