{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T21:30:01Z","timestamp":1772141401279,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"vor","delay-in-days":0,"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":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Recurrent pregnancy loss (RPL) is a common disease characterized by immune dysfunction and vitamin D deficiency. This study aimed to investigate vitamin D metabolism and \u03b3\u03b4T cell phenotypes at the maternal\u2013fetal interface in women with early normal pregnancy (NP) and RPL and to determine the effects of vitamin D on the functions of \u03b3\u03b4T cells and their crosstalk with trophoblasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The levels of 25\u2010(OH)VD<jats:sub>3<\/jats:sub>, the expression of vitamin D metabolic enzymes in the villi, and the proportion of \u03b3\u03b4T cells in the decidua were detected in women with NP and RPL. After treatment with different concentrations of vitamin D, the mRNA expression of the vitamin D receptor (<jats:italic>VDR<\/jats:italic>), cytokines, and transcription factors were detected in V\u03b42<jats:sup>+<\/jats:sup>\u03b3\u03b4T cells. In addition, the proliferation, migration, and invasion of HTR\u20108\/SVneo trophoblasts were determined by coculturing them with vitamin D\u2010treated V\u03b42<jats:sup>+<\/jats:sup>\u03b3\u03b4T cells and their supernatants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In women with RPL, the level of 25\u2010(OH)VD<jats:sub>3<\/jats:sub> in the villi was increased; however, that of CYP27B1 (enzyme converting 25\u2010(OH)VD<jats:sub>3<\/jats:sub> into 1,25\u2010(OH)<jats:sub>2<\/jats:sub>VD<jats:sub>3<\/jats:sub>) was decreased. In addition, the proportion of V\u03b42<jats:sup>+<\/jats:sup>\u03b3\u03b4T cells increased, whereas that of Foxp3<jats:sup>+<\/jats:sup>V\u03b42<jats:sup>+<\/jats:sup>\u03b3\u03b4T cells decreased in the decidua of women with RPL. An in vitro study showed that vitamin D increased the expression of <jats:italic>VDR<\/jats:italic> mRNA and Foxp3, but decreased the expression of <jats:italic>IFN\u2010\u03b3<\/jats:italic> mRNA, in V\u03b42<jats:sup>+<\/jats:sup>\u03b3\u03b4T cells. Finally, vitamin D\u2010treated V\u03b42<jats:sup>+<\/jats:sup>\u03b3\u03b4T cells promoted trophoblast migration and invasion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Abnormal vitamin D metabolism and \u03b3\u03b4T cell proportions were present at the maternal\u2010fetal interface in women with RPL. Under normal pregnancy conditions, vitamin D can induce the differentiation of decidual V\u03b42<jats:sup>+<\/jats:sup>\u03b3\u03b4T cells toward an anti\u2010inflammatory phenotype (Treg\u2010like \u03b3\u03b4T cells) and modulate the crosstalk between V\u03b42<jats:sup>+<\/jats:sup>\u03b3\u03b4T cells and trophoblasts.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13581","type":"journal-article","created":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T17:41:50Z","timestamp":1655314910000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Altered vitamin D metabolism is involved in the dysregulation of \u03b3\u03b4T cell function and their crosstalk with trophoblasts in recurrent pregnancy loss"],"prefix":"10.1111","volume":"89","author":[{"given":"Qian\u2010Han","family":"Xu","sequence":"first","affiliation":[{"name":"Institute of Reproductive Health Center for Reproductive Medicine Tongji Medical College Huazhong University of Science and Technology  Wuhan P.R. 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