{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:05:19Z","timestamp":1789452319160,"version":"build-2803163510"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Nutrient availability critically governs group 2 innate lymphoid cell (ILC2) function and type 2 immunity. Here, we identify the non-essential amino acid asparagine (Asn) as a critical metabolite required for ILC2 survival and function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>Asns<\/jats:italic>\n                      deletion, dietary Asn restriction, and\n                      <jats:italic>Nippostrongylus brasiliensis<\/jats:italic>\n                      infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>Asns<\/jats:italic>\n                      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\n                      <jats:italic>Asns<\/jats:italic>\n                      deficiency. During\n                      <jats:italic>N. brasiliensis<\/jats:italic>\n                      infection, reduced intestinal Asn availability enhanced ILC2 reliance on Asns, whose deficiency impaired ILC2 abundance in the mLNs and protective anti-helminth immunity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings identify Asn as a context-dependent metabolic adaptor that supports ILC2 viability and function under nutrient-limited and type 2 inflammatory conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1878920","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:36:19Z","timestamp":1789450579000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["ASNS-dependent asparagine availability supports intestinal ILC2 responses and type 2 immunity under nutrient-limited conditions"],"prefix":"10.3389","volume":"17","author":[{"given":"Wenyu","family":"Tian","sequence":"first","affiliation":[{"name":"Advanced Medical Research Institute, Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Liu","sequence":"additional","affiliation":[{"name":"Advanced Medical Research Institute, Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Qilu Hospital of Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Shen","sequence":"additional","affiliation":[{"name":"Advanced Medical Research Institute, Shandong University","place":["Jinan, China"]},{"name":"Suzhou Research Institute of Shandong 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