{Reference Type}: Journal Article
{Title}: mTOR aggravated CD4+ T cell pyroptosis by regulating the PPARγ-Nrf2 pathway in sepsis.
{Author}: Zhao G;Xie Y;Lei X;Guo R;Cui N;
{Journal}: Int Immunopharmacol
{Volume}: 140
{Issue}: 0
{Year}: 2024 Oct 25
{Factor}: 5.714
{DOI}: 10.1016/j.intimp.2024.112822
{Abstract}: Sepsis is a systemic inflammatory response syndrome caused by a dysregulated host response to infection. CD4+T cell reduction is crucial to sepsis-induced immunosuppression. Pyroptosis, a programmed necrosis, is concerned with lymphocytopenia. Peroxisome proliferator-activated receptor gamma (PPARγ) regulated by upstream mTOR, exerts anti-pyroptosis effects. To investigate the potential effects of mTOR-PPARγ on sepsis-induced CD4+T cell depletion and the underlying mechanisms, we observed mTOR activation and pyroptosis with PPARγ-Nrf suppression through cecal ligation and puncture (CLP) sepsis mouse model. Further mechanism research used genetically modified mice with T cell-specific knockout mTOR or Tuberous Sclerosis Complex1 (TSC1). It revealed that mTOR mediated CD4 + T cell pyroptosis in septic mice by negatively regulating the PPARγ-Nrf2 signaling pathway. Taken together, mTOR-PPARγ-Nrf2 signaling mediated the CD4+ T cell pyroptosis in sepsis, contributing to CD4+T cell depletion and immunosuppression.