| First Author | Guo R | Year | 2023 |
| Journal | Int Immunopharmacol | Volume | 124 |
| Issue | Pt B | Pages | 110964 |
| PubMed ID | 37738689 | Mgi Jnum | J:344268 |
| Mgi Id | MGI:7538710 | Doi | 10.1016/j.intimp.2023.110964 |
| Citation | Guo R, et al. (2023) Depletion of mTOR ameliorates CD(4)(+) T cell pyroptosis by promoting autophagy activity in septic mice. Int Immunopharmacol 124(Pt B):110964 |
| abstractText | A reduction in the number of CD(4)(+) T cells is a central part of the immunosuppression phase of sepsis and leads to impaired immune defense ability and increased mortality. Pyroptosis, a newly discovered programmed cell death, was confirmed to be an important mechanism of lymphocytopenia in a lot of human diseases and is under the regulation of autophagy. The mammalian target of rapamycin (mTOR) pathway is closely related to CD(4)(+) T-cell survival. Whether the mTOR pathway influences CD(4)(+) T cell pyroptosis by regulating autophagy remains unknown. In this study, a septic mouse model was developed using cecal ligation and puncture (CLP) to explore the degree of pyroptosis and autophagy of CD(4)(+) T cells. T-cell-specific mTOR/TSC1-knockout mice were used to investigate the role of mTOR pathway in the regulation of CD(4)(+) 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 CD(4)(+) 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 CD(4)(+) 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 CD(4)(+) 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. |
