Amino acid availability acts as a metabolic rheostat to determine the magnitude of ILC2 responses

Group 2 innate lymphoid cells (ILC2) are functionally poised, tissue-resident lymphocytes that respond rapidly to damage and infection at mucosal barrier sites. ILC2 reside within complex microenvironments where they are subject to cues from both the diet and invading pathogens-including helminths. Emerging evidence suggests ILC2 are acutely sensitive not only to canonical activating signals but also perturbations in nutrient availability. In the context of helminth infection, we identify amino acid availability as a nutritional cue in regulating ILC2 responses. ILC2 are found to be uniquely preprimed to import amino acids via the large neutral amino acid transporters Slc7a5 and Slc7a8. Cell-intrinsic deletion of these transporters individually impaired ILC2 expansion, while concurrent loss of both transporters markedly impaired the proliferative and cytokine-producing capacity of ILC2. Mechanistically, amino acid uptake determined the magnitude of ILC2 responses in part via tuning of mTOR. These findings implicate essential amino acids as a metabolic requisite for optimal ILC2 responses within mucosal barrier tissues. Here, Hodge et al. demonstrate large neutral amino acid transporters regulate the magnitude of ILC2 responses. Amino acid uptake controls ILC2 expansion in part via mTOR. These findings expand understanding of nutrient regulation of innate immunity at mucosal barrier sites.

Automated summary

ILC2 are tissue-resident lymphocytes that respond rapidly to damage and infection at mucosal barrier sites. They are sensitive to cues from the diet and invading pathogens, and also to perturbations in nutrient availability. Amino acid availability has been identified as a nutritional cue in regulating ILC2 responses.