PR001948 (Project)

Description:Metabolism has a profound impact on T cell fate and function. Uncovering the metabolome of circulating human CD4+ T effector memory (Teff) and T regulatory (Treg) cells would enable better understanding of Th2-driven diseases, such as allergy or asthma. Here, we demonstrated that in healthy humans, energy metabolism and functions of memory CD4+ Teff cells mainly relied on amino acids, whereas Treg cells predominantly used fatty acids. Arginine and phenylalanine increased T cell receptorinduced glycolysis and oxidative phosphorylation in total and memory CD4+ T cells, but high levels of phenylalanine limited CD4+ T cell proliferation via disrupting mitochondrial respiration and activation of L-phenylalanine oxidase, IL4I1. Accordingly, lowest levels of phenylalanine were linked with the pathogenic Th2a cells, and impaired Treg cells in patients with the most severe forms of allergies. It all suggests that phenylalanine is a metabolic checkpoint of pathogenic Th2 cells development.