L-Phenylalanine is a metabolic checkpoint of human Th2 cells.

ABSTRACT: After the primary response, circulating memory CD4⁺T effector and T regulatory (Treg) cells regulate recall responses, typically impaired in allergy. We discovered distinct metabolomes of these cells in humans, differentially enriched in phenylalanine-related metabolites. Energy metabolism assessment in in vitro and ex vivo single-cell analyses revealed that increased intracellular L-phenylalanine boosts glycolysis while limiting oxidative phosphorylation (OXPHOS) in CD4⁺T, memory CD4⁺T, and Th2 cells, but not in Th1, Th17, or Treg cells. L-phenylalanine also restrains proliferation of memory CD4⁺T, Th2, and Th17 cells in an IL4I1-dependent manner and limits Th2 differentiation via inhibition of STAT6 and mechanistic target of rapamycin (mTOR) si

SUBMITTER: Kulkarni AJ 

PROVIDER: S-EPMC12765850 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature