Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation

Gerdien Mijnheer, Lisanne Lutter, Michal Mokry, Marlot van der Wal, Rianne Scholman, Veerle Fleskens, Aridaman Pandit, Weiyang Tao, Mark Wekking, Stephin Vervoort, Ceri Roberts, Alessandra Petrelli, Janneke G C Peeters, Marthe Knijff, Sytze de Roock, Sebastiaan Vastert, Leonie S Taams, Jorg van Loosdregt, Femke van Wijk

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
10 Downloads (Pure)

Abstract

Treg cells are critical regulators of immune homeostasis, and environment-driven Treg cell differentiation into effector (e)Treg cells is crucial for optimal functioning. However, human Treg cell programming in inflammation is unclear. Here, we combine transcriptional and epigenetic profiling to identify a human eTreg cell signature. Inflammation-derived functional Treg cells have a transcriptional profile characterized by upregulation of both a core Treg cell (FOXP3, CTLA4, TIGIT) and effector program (GITR, BLIMP-1, BATF). We identify a specific human eTreg cell signature that includes the vitamin D receptor (VDR) as a predicted regulator in eTreg cell differentiation. H3K27ac/H3K4me1 occupancy indicates an altered (super-)enhancer landscape, including enrichment of the VDR and BATF binding motifs. The Treg cell profile has striking overlap with tumor-infiltrating Treg cells. Our data demonstrate that human inflammation-derived Treg cells acquire a conserved and specific eTreg cell profile guided by epigenetic changes, and fine-tuned by environment-specific adaptations.

Original languageEnglish
Article number2710
Pages (from-to)1-16
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - Dec 2021

Keywords

  • Adolescent
  • Arthritis, Juvenile/genetics
  • Base Sequence
  • Basic-Leucine Zipper Transcription Factors/genetics
  • CTLA-4 Antigen/genetics
  • Case-Control Studies
  • Cell Differentiation
  • Child
  • Child, Preschool
  • Epigenesis, Genetic
  • Female
  • Forkhead Transcription Factors/genetics
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Glucocorticoid-Induced TNFR-Related Protein/genetics
  • Histones/genetics
  • Humans
  • Joints/immunology
  • Male
  • Metabolic Networks and Pathways/genetics
  • Positive Regulatory Domain I-Binding Factor 1/genetics
  • Primary Cell Culture
  • Receptors, Calcitriol/genetics
  • Receptors, Immunologic/genetics
  • T-Lymphocytes, Regulatory/immunology
  • Transcriptome
  • Young Adult

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