ATF4 Regulates CD4⁺ T Cell Immune Responses through Metabolic Reprogramming.

ABSTRACT: T cells are strongly regulated by oxidizing environments and amino acid restriction. How T cells reprogram metabolism to adapt to these extracellular stress situations is not well understood. Here, we show that oxidizing environments and amino acid starvation induce ATF4 in CD4⁺ T cells. We also demonstrate that Atf4-deficient CD4⁺ T cells have defects in redox homeostasis, proliferation, differentiation, and cytokine production. We further reveal that ATF4 regulates a coordinated gene network that drives amino acid intake, mTORC1 activation, protein translation, and an anabolic program for de novo synthesis of amino acids and glutathione. ATF4 also promotes catabolic glycolysis and glutaminolysis and oxidative phosphorylation and thereby provides precursors and energ

SUBMITTER: Yang X 

PROVIDER: S-EPMC6051420 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature