{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T08:48:10Z","timestamp":1769071690803,"version":"3.49.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>A unique immunotolerant microenvironment with Th2 bias in the decidua provides an essential security for successful pregnancy. The disorganized maternal-fetal immune tolerance contributes to more than 50% of unexplained recurrent spontaneous abortion (RSA). How the Th2 bias is developed at the maternal-fetal interface remains undefined. NR2F2, a member of steroid\/thyroid nuclear receptor superfamily, is endowed with diverse importance in cell-fate specification, organogenesis, angiogenesis, and metabolism. Here, we showed that NR2F2 was absolutely highly expressed in decidual CD4<jats:sup>+<\/jats:sup>T(dCD4<jats:sup>+<\/jats:sup>T) cells, but not in peripheral circulating CD4<jats:sup>+<\/jats:sup>T cells during early pregnancy. Decidual NR2F2-expressing CD4<jats:sup>+<\/jats:sup>T cells dominantly produced Th2 cytokines. In unexplained RSA patients, NR2F2 expression in dCD4<jats:sup>+<\/jats:sup>T cells was significantly decreased, accompanied with disordered phenotype of dCD4<jats:sup>+<\/jats:sup>T cells. Furthermore, overexpression of NR2F2 promoted the Th2 differentiation of naive CD4<jats:sup>+<\/jats:sup>T cells. Immunoprecipitation experiment confirmed the binding relationship between GATA-3 and NR2F2, which implied GATA-3 may be an important interactive element involved in the immunoregulatory process of NR2F2. This study is the first to reveal a previously unappreciated role for NR2F2-mediated dCD4<jats:sup>+<\/jats:sup>T cells in maternal-fetal immune tolerance and maintenance of normal pregnancy, in the hope of providing a potential biomarker for prediction and prevention of clinical unexplained RSA.<\/jats:p>","DOI":"10.3389\/fimmu.2021.670777","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T14:27:45Z","timestamp":1621348065000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Decidual NR2F2-Expressing CD4+ T Cells Promote TH2 Transcriptional Program During Early 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