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Although the effects of glutamate on the immune system have been reported previously, its role in modulating the function of ILC2s and lung inflammation remains unclear.<\/jats:p>\n                  <jats:p>\n                    In this study, we report that the glutamate levels increased in lung tissue following exposure to allergens. Consequently, glutamate was found to restrain ILC2 responses during lung inflammation in mice. Using Rag1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, we demonstrated that the inhibitory effect of glutamate on type 2 inflammation was independent of T and B cells. Further ILC2 adoptive transfer experiments in Rag\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    Il2rg\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    \u00a0mice confirmed that glutamate likely exerted its effects by directly targeting ILC2s. In vitro experiments revealed that glutamate suppressed ILC2 function through ionic kainate receptor signaling. Genetic deletion of the kainate receptor subunit GluK2 enhanced ILC2 responses and exacerbated type 2 lung inflammation. Mechanistically, transcriptome and metabolic analyses revealed that glutamate reduced oxidative metabolism in ILC2s, thereby limiting their activation. Consistently, in vivo administration of BPAM344\u2014a positive allosteric modulator that potentiates GluK2 signaling\u2014effectively suppressed allergen-induced type 2 inflammation. Notably, ILC2-specific GluK2 deletion markedly attenuated the anti-inflammatory effects of BPAM344, indicating that its protective effects depend on ILC2-intrinsic GluK2 signaling.\n                  <\/jats:p>\n                  <jats:p>These findings demonstrate a novel role for glutamate in restraining ILC2 function, as it plays a protective role in alleviating airway inflammation. We propose that GluK2 activation may offer a promising therapeutic strategy for treating ILC2-driven allergic asthma.<\/jats:p>","DOI":"10.1038\/s41423-026-01461-4","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:47:35Z","timestamp":1792147655000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glutamate attenuates the ILC2 response and allergic airway inflammation via the kainate receptor GluK2"],"prefix":"10.1038","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5697-7396","authenticated-orcid":false,"given":"Bo","family":"Peng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siying","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5307-8572","authenticated-orcid":false,"given":"Shufen","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xixi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2417-6516","authenticated-orcid":false,"given":"Yaguang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huacheng","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1107-2646","authenticated-orcid":false,"given":"Yuying","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianye","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guochao","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"key":"1461_CR1","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1016\/j.cell.2021.02.016","volume":"184","author":"H Hammad","year":"2021","unstructured":"Hammad H, Lambrecht BN. 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