AUTHOR=Tsuda Sayaka , Shichino Shigeyuki , Tilburgs Tamara , Shima Tomoko , Morita Keiko , Yamaki-Ushijima Akemi , Roskin Krishna , Tomura Michio , Sameshima Azusa , Saito Shigeru , Nakashima Akitoshi 

TITLE=CD4+ T cell heterogeneity in gestational age and preeclampsia using single-cell RNA sequencing

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1401738

DOI=10.3389/fimmu.2024.1401738

ISSN=1664-3224

ABSTRACT=<p>A balance between pro-inflammatory decidual CD4<sup>+</sup> T cells and <italic>FOXP3<sup>+</sup></italic> regulatory T cells (<italic>FOXP3<sup>+</sup></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<sup>+</sup> T cell subsets depend on gestational age. Th1/Th2 intermediate and Th1 subsets of CD4<sup>+</sup> T cells were clonally expanded in both early and late gestation, whereas <italic>FOXP3<sup>+</sup></italic> Tregs were clonally expanded in late gestation. Th1/Th2 intermediate and <italic>FOXP3<sup>+</sup></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 <italic>FOXP3<sup>+</sup></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.</p>