SLC7A8 is essential for metabolic fitness and function of Th2 cells

Amino acids are essential for the activation and function of CD4 T helper cells (Th), whichdifferentiate into Th1, Th2, Th17, and Treg subsets to coordinate immune responses.While specific amino acid transporters have been identified for Th1, Th17, and Tregs, atransporter regulating Th2 cells remains unknown. This study identifies SLC7A8 as a Th2-specific amino acid transporter in the Th compartment. We found that Slc7a8 expressionis upregulated in Th2 cells compared to other T helper subsets, and Slc7a8 deficiencyimpairs Th2 cell proliferation and cytokine production. Furthermore, SLC7A8 was foundto be crucial for an effective type 2 immune response to helminth infection and allergen induced lung inflammation. Mechanistically, Slc7a8 deficiency disrupted Th2 cellmetabolism, leading to reduced mTOR activation and, consequently, diminishedmitochondrial function along with an impaired c-Myc pathway; these defects cumulativelyinduced cellular stress that curtailed cell growth and survival. Collectively, these findingshighlight a previously unknown role for SLC7A8 in Th2 cells, with potential implicationsfor understanding and treating type 2 immune-related diseases.