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CX3CR1 and CCR5 had the highest expression on the effector\u2010memory T\u2010cell (T\n EM<\/jats:sub>\n ) subset in the blood, with expression consistent across subsets in decidua. CD126\/IL\u20106R was lower in pregnant blood and decidual CD4\n +<\/jats:sup>\n T\u00a0cells, while scRNAseq identified enrichment in the IL\u20106R signalling pathway in naive CD4\n +<\/jats:sup>\n T\u00a0cells in pregnant blood. Both sIL\u20106R and IL\u20106 concentrations were increased in plasma during pregnancy, suggesting perturbations to the IL\u20106\/IL\u20106R signalling axis. Meanwhile, decidual CD4\n +<\/jats:sup>\n T\u00a0cells had increased expression of transcription factor RUNX3 in the CD69\n +<\/jats:sup>\n tissue\u2010resident\u2010like subset.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our findings demonstrate altered molecular expression in CD4\n +<\/jats:sup>\n T\u00a0cells during pregnancy. This provides important mechanistic insight of their adaptation and regulation during placental development, which may drive placental dysfunction or pregnancy complications, including preeclampsia, fetal growth restriction and stillbirth. These new data may inform future studies that focus on determining the significance of differentially expressed immune features in pregnancy to identify potential targets for immune modulation to treat pregnancy complications and infections.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cti2.70096","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T06:13:26Z","timestamp":1777443206000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["High\u2010dimensional multiomics reveals perturbations to\n IL<\/scp>\n \u20106\/\n IL<\/scp>\n \u2010\n 6R<\/scp>\n axis and\n RUNX3<\/scp>\n in\n CD4<\/scp>\n +<\/sup>\n T\u00a0cells during third\u2010trimester pregnancy"],"prefix":"10.1002","volume":"15","author":[{"given":"Jennifer R","family":"Habel","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi H O","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"de Alwis","sequence":"additional","affiliation":[{"name":"The Department of Obstetrics, Gynaecology and Newborn Health University of Melbourne Heidelberg VIC Australia"},{"name":"Mercy Perinatal Mercy Hospital for Women Heidelberg VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E Kaitlynn","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Immunology St. Jude Children's Research Hospital Memphis TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihan","family":"Li","sequence":"additional","affiliation":[{"name":"Computational Sciences Initiative, Department of Immunology and Microbiology University of Melbourne at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan J","family":"Skinner","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A","family":"Juno","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8539-4891","authenticated-orcid":false,"given":"Stephen J","family":"Kent","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Bond","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia"},{"name":"Department of Microbiology Royal Melbourne Hospital Parkville VIC Australia"},{"name":"Victorian Infectious Diseases Service Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A","family":"Williamson","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia"},{"name":"Victorian Infectious Diseases Service Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia"},{"name":"Department of Infectious Diseases The University of Melbourne at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia"},{"name":"School of Medicine University of St Andrews St Andrews SCT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Lappas","sequence":"additional","affiliation":[{"name":"The Department of Obstetrics, Gynaecology and Newborn Health University of Melbourne Heidelberg VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie J","family":"Hannan","sequence":"additional","affiliation":[{"name":"The Department of Obstetrics, Gynaecology and Newborn Health University of Melbourne Heidelberg VIC Australia"},{"name":"Mercy Perinatal Mercy Hospital for Women Heidelberg VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Walker","sequence":"additional","affiliation":[{"name":"The Department of Obstetrics, Gynaecology and Newborn Health University of Melbourne Heidelberg VIC Australia"},{"name":"Mercy Perinatal Mercy Hospital for Women Heidelberg VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Computational Sciences Initiative, Department of Immunology and Microbiology University of Melbourne at the Peter Doherty Institute for Infection and Immunity Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy Chase","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Host\u2010Microbe 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