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

First Author  Hodge SH Year  2023
Journal  J Exp Med Volume  220
Issue  3 PubMed ID  36571761
Mgi Jnum  J:333885 Mgi Id  MGI:7413840
Doi  10.1084/jem.20221073 Citation  Hodge SH, et al. (2023) Amino acid availability acts as a metabolic rheostat to determine the magnitude of ILC2 responses. J Exp Med 220(3)
abstractText  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.
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