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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. [ABSTRACT FROM AUTHOR]

Introduction. When sepsis attacks the body, the excessive reactive oxygen species (ROS) production can result to endoplasmic reticulum stress (ERS) and eventually cause lymphocyte apoptosis. The mammalian target of rapamycin (mTOR) is essential for regulating lymphocyte apoptosis; we hypothesized that it mediates CD4+ T cell apoptosis during ROS-related ERS. Method. We, respectively, used ROS and ERS blockers to intervene septic mice and then detected ERS protein expression levels to verify the relationship between them. Additionally, we constructed T cell-specific mTOR and TSC1 gene knockout mice to determine the role of mTOR in ROS-mediated, ERS-induced CD4+ T cell apoptosis. Results. Blocking ROS significantly suppressed the CD4+ T cell apoptosis associated with the reduction in ERS, as revealed by lower levels of GRP78 and CHOP. ERS rapidly induced mTOR activation, leading to the induction of CD4+ T cell apoptosis. However, mTOR knockout mice displayed reduced expression of apoptotic proteins and less ER vesiculation and expansion than what was observed in the wild-type sepsis controls. Conclusion. By working to alleviate ROS-mediated, ERS-induced CD4+ T cell apoptosis, the mTOR pathway is vital for CD4+ T cell survival in sepsis mouse model. [ABSTRACT FROM AUTHOR]

Introduction: When sepsis attacks the body, the excessive reactive oxygen species (ROS) production can result to endoplasmic reticulum stress (ERS) and eventually cause lymphocyte apoptosis. The mammalian target of rapamycin (mTOR) is essential for regulating lymphocyte apoptosis; we hypothesized that it mediates CD4 + T cell apoptosis during ROS-related ERS., Method: We, respectively, used ROS and ERS blockers to intervene septic mice and then detected ERS protein expression levels to verify the relationship between them. Additionally, we constructed T cell-specific mTOR and TSC1 gene knockout mice to determine the role of mTOR in ROS-mediated, ERS-induced CD4 + T cell apoptosis., Results: Blocking ROS significantly suppressed the CD4 + T cell apoptosis associated with the reduction in ERS, as revealed by lower levels of GRP78 and CHOP. ERS rapidly induced mTOR activation, leading to the induction of CD4 + T cell apoptosis. However, mTOR knockout mice displayed reduced expression of apoptotic proteins and less ER vesiculation and expansion than what was observed in the wild-type sepsis controls., Conclusion: By working to alleviate ROS-mediated, ERS-induced CD4 + T cell apoptosis, the mTOR pathway is vital for CD4 + T cell survival in sepsis mouse model., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Hao Wang et al.)