mTOR aggravated CD4⁺ T cell pyroptosis by regulating the PPARγ-Nrf2 pathway in sepsis

Area of Science:

• Immunology
• Cell Biology
• Molecular Medicine

Background:

• Sepsis involves a systemic inflammatory response due to infection.
• CD4+ T cell reduction is a key factor in sepsis-induced immunosuppression.
• Pyroptosis, a form of programmed necrosis, contributes to lymphocytopenia in sepsis.

Purpose of the Study:

• To investigate the role of the mTOR-PPARγ pathway in sepsis-induced CD4+ T cell depletion.
• To elucidate the underlying molecular mechanisms connecting mTOR, PPARγ, and T cell pyroptosis in sepsis.

Main Methods:

• Cecal ligation and puncture (CLP) sepsis mouse model.
• Observation of mTOR activation, pyroptosis, and PPARγ-Nrf2 suppression.
• Utilized genetically modified mice with T cell-specific knockout of mTOR or TSC1.

Main Results:

• mTOR activation was observed in septic mice.
• mTOR negatively regulated the PPARγ-Nrf2 signaling pathway.
• mTOR mediated CD4+ T cell pyroptosis in septic mice.

Conclusions:

• The mTOR-PPARγ-Nrf2 signaling pathway is critical in mediating CD4+ T cell pyroptosis during sepsis.
• Dysregulation of this pathway contributes to CD4+ T cell depletion and immunosuppression in sepsis.
• Targeting the mTOR-PPARγ-Nrf2 pathway may offer therapeutic strategies for sepsis.