{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T23:07:21Z","timestamp":1773702441424,"version":"3.50.1"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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":"U.S. 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":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Prostaglandin I2 (PGI2) is a lipid mediator known to inhibit T helper 2 (Th2) immune responses and allergic inflammation, but its role in regulating Th2 cell metabolism remains underexplored. Using the Seahorse assay, we evaluated the effects of PGI2 signaling on Th2 cell glycolysis and mitochondrial respiration. Our results show that cicaprost, a stable PGI2 analog, significantly reduced basal, maximal, and spare glycolytic capacities in wild-type Th2 cells, while these effects are absent in Th2 cells lacking the PGI2 IP receptor (IP knockout [KO]). Cicaprost also impaired mitochondrial respiration and adenosine triphosphate production in wild-type Th2 cells, but not in IP KO cells, indicating that PGI2 signaling is essential for these metabolic changes. Further analysis revealed that cicaprost decreased glucose transporter 1 expression and glucose uptake and inhibited mitochondrial mass and membrane potential, suggesting that PGI2 signaling inhibits Th2 cell metabolism by reducing glucose availability and mitochondrial respiratory functions. Metabolomic profiling of cicaprost-treated Th2 cells showed dose-dependent changes, with 126 downregulated and 233 upregulated metabolites showing over 2-fold significant changes compared with vehicle-treated cells. Pathway analysis of these altered metabolites suggests a shift from catabolism to anabolism in cicaprost-treated Th2 cells. In vivo, CD4-specific conditional IP KO mice (CD4Cre+IPflox) exhibited exacerbated lung inflammation following exposure to Alternaria alternata extract, marked by increased IL-5 and IL-13 production, enhanced eosinophilia, and elevated mucus production. These findings establish a mechanistic link between PGI2-mediated immunoregulation and metabolic reprogramming, reinforcing its role as a key modulator of allergic inflammation.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf130","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T15:55:21Z","timestamp":1751298921000},"page":"2270-2280","source":"Crossref","is-referenced-by-count":1,"title":["PGI2 signaling metabolically reprograms CD4 Th2 cells and represses allergic airway inflammation"],"prefix":"10.1093","volume":"214","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4419-2302","authenticated-orcid":false,"given":"Weisong","family":"Zhou","sequence":"first","affiliation":[{"name":"Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine , Nashville, TN,","place":["United 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Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine , Nashville, TN,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masako","family":"Abney","sequence":"additional","affiliation":[{"name":"Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine , Nashville, TN,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Rusznak","sequence":"additional","affiliation":[{"name":"Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine , Nashville, TN,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine N","family":"Gibson-Corley","sequence":"additional","affiliation":[{"name":"Division of Comparative Medicine, Vanderbilt University School of Medicine , Nashville, TN,","place":["United States"]},{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine , Nashville, TN,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel P","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa , Iowa City, IA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawn C","family":"Newcomb","sequence":"additional","affiliation":[{"name":"Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine , Nashville, TN,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Ray Stokes","family":"Peebles","sequence":"additional","affiliation":[{"name":"Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine , Nashville, TN,","place":["United States"]},{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine , Nashville, TN,","place":["United States"]},{"name":"Veterans Affairs Tennessee Valley Health Care , Nashville, TN,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"2025093003524996500_vkaf130-B1","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1084\/jem.20151159","article-title":"T cell metabolism drives immunity","volume":"212","author":"Buck","year":"2015","journal-title":"J Exp Med"},{"key":"2025093003524996500_vkaf130-B2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41577-019-0203-y","article-title":"Metabolic coordination of T cell quiescence and activation","volume":"20","author":"Chapman","year":"2020","journal-title":"Nat Rev 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