Depletion of mTOR ameliorates CD < sub > 4 < /sub > < sup > + < /sup > T cell pyroptosis by promoting autophagy activity in septic mice

In this study, a septic mouse model was developed using cecal ligation and puncture (CLP) to explore the degree of pyroptosis and autophagy of CD4+ T cells. T-cell-specific mTOR/TSC1-knockout mice were used to investigate the role of mTOR pathway in the regulation of CD4+ T cell pyroptosis. Bafilomycin, a specific autophagy inhibitor, was used to verify the regulatory effect of autophagy on pyroptosis in septic mice. We observed aggravated pyroptosis in CD4+ T cells in CLP mice accompanied by impaired autophagy activity and an overactivated mTOR signaling pathway. Depletion of mTOR relieved autophagy deficiency and reduced the proportion of pyroptotic CD4+ T cells. In T-cell-specific mTOR-knockout mice treated with bafilomycin, the protective effect of mTOR depletion vanished. This indicated that autophagy negatively regulates CD4+ T cell pyroptosis, which is under the control of the mTOR pathway. Taken together, our findings emphasize the importance of pyroptosis in sepsis-induced lymphopenia and reveal the regulatory effects of the mTOR pathway and the role of autophagy in this regulation.PMID:37738689 | DOI:10.1016/j.intimp.2023.110964

Source: International Immunopharmacology - September 22, 2023 Category: Allergy & Immunology Authors: Ran Guo Guoyu Zhao Guangxu Bai Jianwei Chen Wen Han Na Cui Hao Wang Source Type: research