{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T23:10:13Z","timestamp":1780614613722,"version":"3.54.1"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI124456"],"award-info":[{"award-number":["R01 AI124456"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI145265"],"award-info":[{"award-number":["R01 AI145265"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19 AI095227"],"award-info":[{"award-number":["U19 AI095227"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI111820"],"award-info":[{"award-number":["R01AI111820"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 AI145397"],"award-info":[{"award-number":["R21 AI145397"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Veterans Affairs Biomedical Laboratory Research and Development Service","award":["101BX004299"],"award-info":[{"award-number":["101BX004299"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pulmonary type 2 innate lymphoid cells (ILC2s) exhibit immune memory, termed \u201ctrained immunity,\u201d which enhances their activation following exposure to an independent protease-containing allergen. The role of prostaglandin I2 (PGI2), a cyclooxygenase (COX) pathway metabolite, in modulating these trained ILC2 responses remains unclear. PGI2 acts through its G protein\u2013coupled receptor IP. We hypothesized that IP signaling inhibits ILC2 training. To test this hypothesis, we used a mouse ILC2 training model in which we challenged wild-type (WT) and IP knockout (KO) mice with Alternaria alternata extract (Alt) to induce ILC2 activation and training. After a 33-d resting period, ILC2 responses subsided to a homeostatic level. Mice were then intranasally challenged with papain to evaluate responses to an unrelated allergen. IP KO mice displayed significantly heightened ILC2 interleukin (IL)-13 expression and with concomitant increased eosinophilia in the lungs post\u2013papain challenge compared with WT control mice. Notably, neither WT nor IP KO mice challenged with papain only, devoid of ILC2 training, exhibited lung type 2 responses. The augmented type 2 inflammation observed in IP KO mice following both Alt and papain challenges correlated with increased numbers and percentages of IL-13-producing ILC2s and greater mean fluorescence intensity of IL-13 compared with WT mice. Furthermore, RNA sequencing of sorted ILC2s from WT and IP KO mice following Alt-papain challenges revealed heightened activation of immune response pathways and mitochondrial respiratory pathways in IP-deficient ILC2s. These findings reveal an inhibitory role of PGI2 signaling in trained ILC2 responses, emphasizing its pivotal contribution to innate immune responses and allergic inflammation.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf088","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T14:55:24Z","timestamp":1746629724000},"page":"1582-1591","source":"Crossref","is-referenced-by-count":3,"title":["PGI2 restricts trained ILC2 responses in allergic inflammation"],"prefix":"10.1093","volume":"214","author":[{"given":"Weisong","family":"Zhou","sequence":"first","affiliation":[{"name":"Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine , Nashville, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine , Nashville, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9357-485X","authenticated-orcid":false,"given":"Allison E","family":"Norlander","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine , Indianapolis, IN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1152-4454","authenticated-orcid":false,"given":"Daniel P","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa , Iowa City, IA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Toki","sequence":"additional","affiliation":[{"name":"Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine , Nashville, TN,","place":["United 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States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ginger L","family":"Milne","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine , Nashville, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn C","family":"Newcomb","sequence":"additional","affiliation":[{"name":"Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine , Nashville, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1429-7875","authenticated-orcid":false,"suffix":"Jr.","given":"R Stokes","family":"Peebles","sequence":"additional","affiliation":[{"name":"Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine , Nashville, TN,","place":["United States"]},{"name":"VA Tennessee Valley Health Care 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