{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:07:22Z","timestamp":1790233642230,"version":"4.1.0"},"reference-count":75,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T00:00:00Z","timestamp":1720742400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>Preeclampsia (PE) is a hypertensive pregnancy disorder that is a leading cause of maternal and fetal morbidity and mortality characterized by maternal vascular dysfunction, oxidative stress, chronic immune activation, and excessive inflammation. No cure exists beyond delivery of the fetal\u2013placental unit and the mechanisms driving pathophysiology are not fully understood. However, aberrant immune responses have been extensively characterized in clinical studies and shown to mediate PE pathophysiology in animal studies. One pathway that may mediate aberrant immune responses in PE is deficiencies in the IL\u201033 signaling pathway. In this study, we aim to investigate the impact of IL\u201033 signaling inhibition on cNK, T<jats:sub>H<\/jats:sub>17, and T<jats:sub>Reg<\/jats:sub> populations, vascular function, and maternal blood pressure during pregnancy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of Study<\/jats:title><jats:p>In this study, IL\u201033 signaling was inhibited using two different methods: intraperitoneal administration of recombinant ST2 (which acts as a decoy receptor for IL\u201033) and administration of a specific IL\u201033 neutralizing antibody. Maternal blood pressure, uterine artery resistance index, renal and placental oxidative stress, cNK, T<jats:sub>H<\/jats:sub>17, and T<jats:sub>Reg<\/jats:sub> populations, various cytokines, and pre\u2010proendothelin\u20101 levels were measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IL\u201033 signaling inhibition increased maternal blood pressure, uterine artery resistance, placental and renal oxidative stress. IL\u201033 signaling inhibition also increased placental cNK and T<jats:sub>H<\/jats:sub>17 and renal T<jats:sub>H<\/jats:sub>17 cells while decreasing placental T<jats:sub>Reg<\/jats:sub> populations. IL\u201033 neutralization increased circulating cNK and T<jats:sub>H<\/jats:sub>17s and decreased circulating T<jats:sub>Reg<\/jats:sub>s in addition to increasing pre\u2010proendothelin\u20101 levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Data presented in this study demonstrate a role for IL\u201033 signaling in controlling vascular function and maternal blood pressure during pregnancy possibly by mediating innate and adaptive immune inflammatory responses, identifying the IL\u201033 signaling pathway as a potential therapeutic target for managing preeclampsia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13895","type":"journal-article","created":{"date-parts":[[2024,7,13]],"date-time":"2024-07-13T05:38:26Z","timestamp":1720849106000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["IL\u201033 Signaling Inhibition Leads to a Preeclampsia\u2010Like Phenotype in Pregnant 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