{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T09:53:51Z","timestamp":1786960431719,"version":"build-2736575974"},"reference-count":73,"publisher":"National Academy of Sciences","issue":"35","license":[{"start":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T00:00:00Z","timestamp":1661126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"HHS | NIH | NIAID | Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI148695"],"award-info":[{"award-number":["AI148695"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000912","name":"March of Dimes Foundation","doi-asserted-by":"publisher","award":["FY20-209"],"award-info":[{"award-number":["FY20-209"]}],"id":[{"id":"10.13039\/100000912","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,8,30]]},"abstract":"<jats:p>\n                    The pregnant uterus is an immunologically rich organ, with dynamic changes in the inflammatory milieu and immune cell function underlying key stages of pregnancy. Recent studies have implicated dysregulated expression of the interleukin-1 (IL-1) family cytokine, IL-33, and its receptor, ST2, in poor pregnancy outcomes in women, including recurrent pregnancy loss, preeclampsia, and preterm labor. How IL-33 supports pregnancy progression in\u00a0vivo is not well understood. Here, we demonstrate that maternal IL-33 signaling critically regulates uterine tissue remodeling and immune cell function during early pregnancy in mice. IL-33\u2013deficient dams exhibit defects in implantation chamber formation and decidualization, and abnormal vascular remodeling during early pregnancy. These defects coincide with delays in early embryogenesis, increased resorptions, and impaired fetal and placental growth by late pregnancy. At a cellular level, myometrial fibroblasts, and decidual endothelial and stromal cells, are the main IL-33\n                    <jats:sup>+<\/jats:sup>\n                    cell types in the uterus during decidualization and early placentation, whereas ST2 is expressed by uterine immune populations associated with type 2 immune responses, including ILC2s, Tregs, CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, M2- and cDC2-like myeloid cells, and mast cells. Early pregnancy defects in IL-33\u2013deficient dams are associated with impaired type 2 cytokine responses by uterine lymphocytes and fewer Arginase-1\n                    <jats:sup>+<\/jats:sup>\n                    macrophages in the uterine microenvironment. Collectively, our data highlight a regulatory network, involving crosstalk between IL-33\u2013producing nonimmune cells and ST2\n                    <jats:sup>+<\/jats:sup>\n                    immune cells at the maternal\u2013fetal interface, that critically supports pregnancy progression in mice. This work has the potential to advance our understanding of how IL-33 signaling may support optimal pregnancy outcomes in women.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2123267119","type":"journal-article","created":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T15:14:57Z","timestamp":1661181297000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":51,"title":["Maternal IL-33 critically regulates tissue remodeling and type 2 immune responses in the uterus during early pregnancy in mice"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6091-6043","authenticated-orcid":false,"given":"Nuriban","family":"Valero-Pacheco","sequence":"first","affiliation":[{"name":"Center for Immunity and Inflammation, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers - The State University of New Jersey, Newark, NJ 07103"},{"name":"Department of Microbiology, Biochemistry, and Molecular Genetics, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers - The State University of New Jersey, Newark, NJ 07103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3899-9668","authenticated-orcid":false,"given":"Eric K.","family":"Tang","sequence":"additional","affiliation":[{"name":"Center for Immunity and Inflammation, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers - The State University of New Jersey, Newark, NJ 07103"},{"name":"Department of Microbiology, Biochemistry, and Molecular Genetics, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers - The State University of New Jersey, Newark, NJ 07103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1063-8617","authenticated-orcid":false,"given":"Noura","family":"Massri","sequence":"additional","affiliation":[{"name":"Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824"},{"name":"Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, East Lansing, MI 48824"},{"name":"Cell and Molecular Biology Program, Michigan State University, East Lansing, MI 48824"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Loia","sequence":"additional","affiliation":[{"name":"Rutgers School of Graduate Studies, Rutgers - The State University of New Jersey, Newark, NJ 07103"},{"name":"Department of Obstetrics, Gynecology and Reproductive Health, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers - The State University of New Jersey, Newark, NJ 07103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8745-9409","authenticated-orcid":false,"given":"Anat","family":"Chemerinski","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Health, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers - The State University of New Jersey, Newark, NJ 07103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Health, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers - The State University of New Jersey, Newark, NJ 07103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma","family":"Begum","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Health, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers - 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Kieckbusch, L. M. Gaynor, F. Colucci, Assessment of maternal vascular remodeling during pregnancy in the mouse uterus. J. Vis. Exp. (106), e53534 (2015).","journal-title":"J. Vis. Exp."},{"key":"e_1_3_4_72_2","unstructured":"A. M. Beaulieu N. Valero-Pacheco IL-33+ cell subsets in the decidua and myometrium of pregnant mice at E7.5. Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE209795. Deposited 26 July 2022."},{"key":"e_1_3_4_73_2","unstructured":"A. M. Beaulieu N. Valero-Pacheco Immune cell distribution in the decidua and myometrium of pregnant mice at E7.5). Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE209796. 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