AMP-activated protein kinase is necessary for Treg cell functional adaptation to microenvironmental stress

• DOI: 10.1101/2023.11.29.568904
• Publication Date: 2023-12-01T20:30:15Z
• Authors: Manuel A Torres A...; Nurbek Mambetsariev; Carla P Reyes Flores; Kathryn A Helmin; Qianli Liu; Anthony M Joudi; Luisa Morales-Neb...; Jonathan Gurkan; Kathleen Cheng; Hiam Abdala-Valencia; Samuel E Weinberg; Benjamin D Singer
• Keywords: AMP-Activated Protein Kinase

CD4+FOXP3+ regulatory T (Treg) cells maintain self-tolerance, suppress the immune response to cancer, and protect against tissue injury in lung other organs. Treg require mitochondrial metabolism exert their function, but how adapt metabolic programs sustain optimize function during an occurring a metabolically stressed microenvironment remains unclear. Here, we tested whether energy homeostasis-maintaining enzyme AMP-activated protein kinase (AMPK) aberrant microenvironments caused by malignancy or injury, finding that AMPK is dispensable for cell immune-homeostatic necessary full B16 melanoma tumors acute influenza virus pneumonia. AMPK-deficient had lower mass exhibited impaired ability maximize aerobic respiration. Mechanistically, found regulates DNA methyltransferase 1 promote transcriptional associated with tumor microenvironment. In viral pneumonia, sustains homeostasis activity. Induction of hypomethylation was sufficient rescue cells, linking methylation metabolism. These results define as determinant adaptation stress offer potential therapeutic targets cancer injury.