{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:37:48Z","timestamp":1792460268093,"version":"4.5.0"},"reference-count":221,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Preterm labor commonly precedes preterm birth, the leading cause of perinatal morbidity and mortality worldwide. Most research has focused on establishing a causal link between innate immune activation and pathological inflammation leading to preterm labor and birth. However, the role of maternal effector\/activated T cells in the pathogenesis of preterm labor\/birth is poorly understood. In this study, we first demonstrated that effector memory and activated maternal T cells expressing granzyme B and perforin are enriched at the maternal-fetal interface (decidua) of women with spontaneous preterm labor. Next, using a murine model, we reported that prior to inducing preterm birth, in vivo T cell activation caused maternal hypothermia, bradycardia, systemic inflammation, cervical dilation, intra-amniotic inflammation, and fetal growth restriction, all of which are clinical signs associated with preterm labor. In vivo T cell activation also induced B cell cytokine responses, a proinflammatory macrophage polarization, and other inflammatory responses at the maternal-fetal interface and myometrium in the absence of an increased influx of neutrophils. Finally, we showed that treatment with progesterone can serve as a strategy to prevent preterm labor\/birth and adverse neonatal outcomes by attenuating the proinflammatory responses at the maternal-fetal interface and cervix induced by T cell activation. Collectively, these findings provide mechanistic evidence showing that effector and activated T cells cause pathological inflammation at the maternal-fetal interface, in the mother, and in the fetus, inducing preterm labor and birth and adverse neonatal outcomes. Such adverse effects can be prevented by treatment with progesterone, a clinically approved strategy.<\/jats:p>","DOI":"10.4049\/jimmunol.1801350","type":"journal-article","created":{"date-parts":[[2019,3,27]],"date-time":"2019-03-27T23:55:16Z","timestamp":1553730916000},"page":"2585-2608","source":"Crossref","is-referenced-by-count":132,"title":["Effector and Activated T Cells Induce Preterm Labor and Birth That Is Prevented by Treatment with Progesterone"],"prefix":"10.1093","volume":"202","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1178-6112","authenticated-orcid":false,"given":"Marcia","family":"Arenas-Hernandez","sequence":"first","affiliation":[{"name":"Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services , Detroit, MI 48201"},{"name":"Department of Obstetrics and Gynecology, Wayne State University School of Medicine , Detroit, MI 48201"},{"name":"Departamento de Biomedicina Molecular, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional , Mexico City 07360 ,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4448-5121","authenticated-orcid":false,"given":"Roberto","family":"Romero","sequence":"additional","affiliation":[{"name":"Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services , Detroit, MI 48201"},{"name":"Department of Obstetrics and Gynecology, University of Michigan , Ann Arbor, MI 48109"},{"name":"Department of Epidemiology and Biostatistics, Michigan State University , East Lansing, MI 48824"},{"name":"Center for Molecular Obstetrics and Genetics, Wayne State University , Detroit, MI 48201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xu","sequence":"additional","affiliation":[{"name":"Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services , Detroit, MI 48201"},{"name":"Department of Obstetrics and Gynecology, Wayne State University School of Medicine , Detroit, MI 48201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan","family":"Panaitescu","sequence":"additional","affiliation":[{"name":"Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services , Detroit, MI 48201"},{"name":"Department of Obstetrics and Gynecology, Wayne State University School of Medicine , Detroit, MI 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of Obstetrics and Gynecology, Wayne State University School of Medicine , Detroit, MI 48201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunyoung","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Wayne State University School of Medicine , Detroit, MI 48201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7977-3764","authenticated-orcid":false,"given":"Bogdan","family":"Done","sequence":"additional","affiliation":[{"name":"Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services , Detroit, MI 48201"},{"name":"Department of Obstetrics and Gynecology, Wayne State University School of Medicine , Detroit, MI 48201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia S","family":"Hassan","sequence":"additional","affiliation":[{"name":"Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services , Detroit, MI 48201"},{"name":"Department of Obstetrics and Gynecology, Wayne State University School of Medicine , Detroit, MI 48201"},{"name":"Department of Physiology, Wayne State University School of Medicine , Detroit, MI 48201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaur-Dong","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Wayne State University School of Medicine , Detroit, MI 48201"},{"name":"Department of Physiology, Wayne State University School of Medicine , Detroit, MI 48201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9281-126X","authenticated-orcid":false,"given":"Adi L","family":"Tarca","sequence":"additional","affiliation":[{"name":"Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services , Detroit, MI 48201"},{"name":"Department of Obstetrics and Gynecology, Wayne State University School of Medicine , Detroit, MI 48201"},{"name":"Department of Computer Science, Wayne State University College of Engineering , Detroit, MI 48202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0045-8233","authenticated-orcid":false,"given":"Carmen","family":"Sanchez-Torres","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina Molecular, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional , Mexico City 07360 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