{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T15:36:49Z","timestamp":1776353809502,"version":"3.51.2"},"reference-count":72,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"General Project of Chongqing Natural Science Foundation","award":["CSTB2024NSCQ-MSX0661"],"award-info":[{"award-number":["CSTB2024NSCQ-MSX0661"]}]},{"name":"General Project of Chongqing Natural Science Foundation","award":["CSTB2022NSCQ-MSX0073"],"award-info":[{"award-number":["CSTB2022NSCQ-MSX0073"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The aim of this study was to elucidate the effect of interleukin (IL)-35 on T-cell differentiation and its mechanism. We evaluated the therapeutic effect of IL-35 on acute respiratory distress syndrome using clinical samples and the mouse cecum ligation and puncture model. The effects of IL-35 on regulatory T cells (Tregs) were verified by flow cytometry, immunohistochemistry, and quantitative real-time reverse transcription polymerase chain reaction. Liquid chromatography\u2013mass spectrometry was used to detect the effects of IL-35 on changes in glutamine metabolites and tricarboxylic acid (TCA) circulation. Western blot was used to detect changes in forkhead box protein 3 (Foxp3), key enzymes, and signal transducer and activator of transcription (STAT) phosphorylation subgroup proteins in the presence of cerdulatinib. Finally, A549 cells were treated with EL-4 cell supernatant to explore the effect of cerdulatinib on the therapeutic effect of IL-35 injury. Inflammatory factors decreased, and Foxp3 increased in response to IL-35. In addition, Foxp3 was upregulated in a glutamine-deficient environment, and notably, glutamine-related metabolism and TCA cycle-related substances were altered with the involvement of IL-35. IL-35 upregulated phosphorylation of STAT isoforms, and cerdulatinib reversed it. Finally, the effects of IL-35 on Foxp3, key enzymes, and glutamine metabolite changes were all reversed by cerdulatinib. Our study shows that IL-35 reduces lung inflammation and promotes Treg differentiation. IL-35 affects the glutamine metabolism and the TCA cycle. In addition, we demonstrated that the relevant functions of IL-35 may be mediated by STAT isoform phosphorylation.<\/jats:p>","DOI":"10.1093\/intimm\/dxaf041","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T07:51:21Z","timestamp":1751529081000},"page":"711-727","source":"Crossref","is-referenced-by-count":2,"title":["Interleukin-35 regulates the differentiation of regulatory T cells through the JAK-STAT pathway and influences glutamine metabolism in ARDS"],"prefix":"10.1093","volume":"37","author":[{"given":"Qiao-zhi","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University , Chongqing ,","place":["China"]},{"name":"The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases , Chongqing 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