Mitochondrial fatty acid synthesis and MECR regulate CD4+ T cell function and oxidative metabolism.

ABSTRACT: Imbalanced effector and regulatory CD4+ T cell subsets drive many inflammatory diseases. These T cell subsets rely on distinct metabolic programs, modulation of which differentially affects T cell fate and function. Lipid metabolism is fundamental yet remains poorly understood across CD4+ T cell subsets. Therefore, we performed targeted in vivo CRISPR/Cas9 screens to identify lipid metabolism genes and pathways essential for T cell functions. These screens established mitochondrial fatty acid synthesis genes Mecr, Mcat, and Oxsm as key metabolic regulators. Of these, the inborn error of metabolism gene Mecr was most dynamically regulated. Mecrfl/fl; Cd4cre mice had normal naïve CD4+ and CD8+ T cell numbers, demonstrating that MECR is not essential in homeostatic conditions. However, effect

SUBMITTER: Steiner KK 

PROVIDER: S-EPMC12123211 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature