SLC7A8 is essential for metabolic fitness and function of Th2 cells

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