mTOR Deletion Alleviates CD4+ T‐Cell Dysfunction in Sepsis through Reducing CTLA4 Accumulation Mediated by Rescuing Autophagy

Sepsis has been the leading cause of death in ICU patients. CD4+ T cells are the mainstay of the body’s immune system, and the depletion of CD4+ T cells in sepsis is of great concern. Cytotoxic T lymphocyte‐associated protein 4 (CTLA4) is a negative immunomodulator for T cell activation and degradation through the autophagy‐lysosome pathway. Mammalian target of rapamycin (mTOR) is the most classical upstream regulator of autophagy. With a mouse model of sepsis through cecal ligation and puncture (CLP), T cell specific‐mTOR/tuberous sclerosis complex 1 (TSC1)‐knockout mice, and bafilomycin A1, a specific autophagosome‐lysosome (A‐L) fusion inhibitor, we primarily proved that mTOR could modulate the expression and accumulation of CTLA4 by regulating the onset process of autophagy such as A‐L fusion. Given such a regulatory relationship, targeting mTOR could provide new light to improve immune function in sepsis, and the prospect of using rapamycin in the clinic would be worth exploring further.