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

Gerdien Mijnheer, Lisanne Lutter, Michal Mokry, Marlot Wal, Rianne Scholman, Veerle Fleskens, Aridaman Pandit, Weiyang Tao, Mark Wekking, Stephin Vervoort, Ceri Roberts, Alessandra Petrelli, Janneke G. C. Peeters, Marthe Knijff, Sytze Roock, Sebastiaan Vastert, Leonie S. Taams, Jorg Loosdregt and Femke Wijk ()
Additional contact information
Gerdien Mijnheer: University Medical Center Utrecht, Utrecht University
Lisanne Lutter: University Medical Center Utrecht, Utrecht University
Michal Mokry: University Medical Center Utrecht, Utrecht University
Marlot Wal: University Medical Center Utrecht, Utrecht University
Rianne Scholman: University Medical Center Utrecht, Utrecht University
Veerle Fleskens: School of Immunology & Microbial Sciences, King’s College London
Aridaman Pandit: University Medical Center Utrecht, Utrecht University
Weiyang Tao: University Medical Center Utrecht, Utrecht University
Mark Wekking: University Medical Center Utrecht
Stephin Vervoort: University Medical Center Utrecht, Utrecht University
Ceri Roberts: School of Immunology & Microbial Sciences, King’s College London
Alessandra Petrelli: University Medical Center Utrecht, Utrecht University
Janneke G. C. Peeters: University Medical Center Utrecht, Utrecht University
Marthe Knijff: University Medical Center Utrecht, Utrecht University
Sytze Roock: University Medical Center Utrecht, Utrecht University
Sebastiaan Vastert: University Medical Center Utrecht, Utrecht University
Leonie S. Taams: School of Immunology & Microbial Sciences, King’s College London
Jorg Loosdregt: University Medical Center Utrecht, Utrecht University
Femke Wijk: University Medical Center Utrecht, Utrecht University

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22975-7

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DOI: 10.1038/s41467-021-22975-7

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