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

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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 RNA-sequencing 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 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.

Original languageEnglish
Pages (from-to)1401738
JournalFrontiers in Immunology
Volume15
DOIs
StatePublished - 2024

Keywords

  • Humans
  • Female
  • Pre-Eclampsia/immunology
  • Pregnancy
  • Single-Cell Analysis/methods
  • Gestational Age
  • Adult
  • T-Lymphocytes, Regulatory/immunology
  • Forkhead Transcription Factors/genetics
  • CD4-Positive T-Lymphocytes/immunology
  • Sequence Analysis, RNA
  • T-Lymphocyte Subsets/immunology
  • Th1 Cells/immunology
  • Decidua/immunology

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