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=Volume 15 - 2024

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=A balance between pro-inflammatory decidual CD4 + T cells and FOXP3 + regulatory T cells (FOXP3 + Tregs) is important for maintaining fetomaternal tolerance. Using single-cell RNAsequencing and T cell receptor repertoire analysis, we determined that diversity and clonality of decidual CD4 + T cell subsets depend on gestational age. Th1/Th2 intermediate and Th1 subsets of CD4 + T cells were clonally expanded in both early and late gestation, whereas FOXP3 + Tregs were scRNAseq of decidual T cells clonally expanded in late gestation. Th1/Th2 intermediate and FOXP3 + 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 FOXP3 + 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.