Data Sheet 3_ASNS-dependent asparagine availability supports intestinal ILC2 responses and type 2 immunity under nutrient-limited conditions.csv

Here, we identify the non-essential amino acid asparagine (Asn) as a critical metabolite required for ILC2 survival and function.</p>Methods<p>We investigated the roles of extracellular Asn availability and asparagine synthetase (ASNS)-mediated de novo Asn biosynthesis in ILC2 responses using complementary in vitro and in vivo approaches, including amino acid restriction, ILC2-specific Asns deletion, dietary Asn restriction, and Nippostrongylus brasiliensis infection.</p>Results<p>ASNS, the rate-limiting enzyme for de novo Asn synthesis, was rapidly induced upon ILC2 activation under type 2 inflammatory conditions.

When extracellular Asn was limited, ILC2s depended on ASNS-mediated Asn synthesis fueled by glutamine (Gln). Genetic ablation of Asns was well tolerated under Asnreplete conditions but severely impaired ILC2 viability and overall effector cytokine output upon Asn restriction. Dietary Asn restriction compromised ILC2s, and this effect was further aggravated by Asns deficiency.