Taurine corrects lupus CD4+ T cell imbalance through inhibition of mTORC1 signaling

Abstract

Objective: This study was designed to explore the metabolism features in systemic lupus erythematosus (SLE) and to investigate the role and regulatory mechanism of taurine in the control of CD4+ T cells and the progression of SLE. Methods: Metabolomic profiles of sera from SLE patients and healthy controls (HCs) were analyzed by mass spectrometry. The therapeutic effects of taurine in vivo were observed in resiquimod (R848) induced mice, and the effects of taurine on various functions of CD4+ T cells were examined by flow cytometry. The effect of mTORC1 agonist MHY1485 on the regulatory capacity of taurine was examined in vitro. Results: Both untargeted metabolomics assays and independent sample validation showed that serum levels of taurine were reduced in SLE patients compared to HCs (P<0.0001), which was inversely correlated with disease activity scores (P<0.05). Taurine supplementation relieved the progression of lupus in R848 induced mice, characterized by a decrease in anti-dsDNA (P<0.01) and proteinuria (P<0.05) and a reduction in the severity of nephritis (P<0.05). And, taurine supplementation improved the differentiation of cell subsets such as Th17 (P<0.001) and Treg cells (P<0.001) in these mice. In vitro, taurine suppressed reactive oxygen species production (P<0.001), proliferation (P<0.0001) and senescence (P<0.0001) of mouse spleen cells. The level of pS6 (P<0.0001) but not AKT in CD4+ T was significantly decreased after taurine treatment, while mTORC1 agonists partially blocked the effect of taurine on CD4+ T cells. Conclusion: Taurine may play a therapeutic role by ameliorating CD4+ T cell abnormalities through inhibition of mTORC1 signaling in SLE.