{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T00:43:49Z","timestamp":1793839429689,"version":"4.6.1"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000},"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 balance between pro-inflammatory decidual CD4<jats:sup>+<\/jats:sup> T cells and <jats:italic>FOXP3<jats:sup>+<\/jats:sup><\/jats:italic> regulatory T cells (<jats:italic>FOXP3<jats:sup>+<\/jats:sup><\/jats:italic> Tregs) is important for maintaining fetomaternal tolerance. Using single-cell RNA-sequencing and T cell receptor repertoire analysis, we determined that diversity and clonality of decidual CD4<jats:sup>+<\/jats:sup> T cell subsets depend on gestational age. Th1\/Th2 intermediate and Th1 subsets of CD4<jats:sup>+<\/jats:sup> T cells were clonally expanded in both early and late gestation, whereas <jats:italic>FOXP3<jats:sup>+<\/jats:sup><\/jats:italic> Tregs were clonally expanded in late gestation. Th1\/Th2 intermediate and <jats:italic>FOXP3<jats:sup>+<\/jats:sup><\/jats:italic> Treg subsets showed altered gene expression in preeclampsia (PE) compared to healthy late gestation. The Th1\/Th2 intermediate subset exhibited elevated levels of cytotoxicity-related gene expression in PE. Moreover, increased Treg exhaustion was observed in the PE group, and <jats:italic>FOXP3<jats:sup>+<\/jats:sup><\/jats:italic> Treg subcluster analysis revealed that the effector Treg like subset drove the Treg exhaustion signatures in PE. The Th1\/Th2 intermediate and effector Treg like subsets are possible inflammation-driving subsets in PE.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1401738","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T04:30:49Z","timestamp":1715056249000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["CD4+ T cell heterogeneity in gestational age and preeclampsia using single-cell RNA 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