{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:26:48Z","timestamp":1753878408024,"version":"3.41.2"},"reference-count":56,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T00:00:00Z","timestamp":1519689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"The March of Dimes Prematurity Research Center at Stanford University"},{"name":"The Mary L Johnson Research Fund"},{"name":"The Christopher Hess Research Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2018,5]]},"abstract":"Problem<\/jats:title>Infection during pregnancy can disrupt regulatory\/effector immune system balance, resulting in adverse pregnancy and fetal\u2010neonatal outcomes. Heme oxygenase\u20101 (HO<\/jats:styled-content>\u20101) is a major regulatory enzyme in the immune system. We observed maternal immune response dysregulation during late gestational inflammation (LGI<\/jats:styled-content>), which may be mediated by HO<\/jats:styled-content>\u20101. Here, we extend these studies to examine the immune response of offspring.<\/jats:p><\/jats:sec>Method of study<\/jats:title>Pregnant wild\u2010type (Wt) and HO<\/jats:styled-content>\u20101 heterozygote (Het) dams were treated with lipopolysaccharide (LPS<\/jats:styled-content>) or vehicle at E15.5. Pups\u2019 splenic immune cells were characterized using flow cytometry.<\/jats:p><\/jats:sec>Results<\/jats:title>CD<\/jats:styled-content>3+<\/jats:sup>CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25+<\/jats:sup> (Tregs) and CD<\/jats:styled-content>3+<\/jats:sup>CD<\/jats:styled-content>8+<\/jats:sup> (Teffs) T cells in Wt and Het were similar in control neonates and increased with age. We showed not only age\u2010 but also genotype\u2010specific and long\u2010lasting T\u2010cell dysregulation in pups after maternal LGI<\/jats:styled-content>. The persistent immune dysregulation, mediated by HO<\/jats:styled-content>\u20101 deficiency, was reflected as a decrease in Treg FoxP3 and CD<\/jats:styled-content>3+<\/jats:sup>CD<\/jats:styled-content>8+<\/jats:sup> T cells, and an increase in CD<\/jats:styled-content>4+<\/jats:sup>\/CD<\/jats:styled-content>8+<\/jats:sup> T\u2010cell and Treg\/Teff ratios in Hets compared with Wt juvenile mice after maternal exposure to LGI<\/jats:styled-content>.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Maternal exposure to LGI<\/jats:styled-content> can result in dysregulation of splenic T cells in offspring, especially in those with HO<\/jats:styled-content>\u20101 deficiency. We speculate that these immune alterations are the basis of adverse outcomes in neonates from mothers exposed to low\u2010grade (subclinical) infections.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.12829","type":"journal-article","created":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T09:16:45Z","timestamp":1519723005000},"source":"Crossref","is-referenced-by-count":4,"title":["Heme oxygenase\u20101 deficiency results in splenic T\u2010cell dysregulation in offspring of mothers exposed to late gestational inflammation"],"prefix":"10.1111","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2020-7821","authenticated-orcid":false,"given":"Maide","family":"Ozen","sequence":"first","affiliation":[{"name":"Department of Pediatrics Division of Neonatal and Developmental Medicine Stanford University School of Medicine Stanford CA USA"},{"name":"Department of Pediatrics Johns Hopkins University Baltimore MD 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