| Literature DB >> 33976194 |
Gerdien Mijnheer1, Lisanne Lutter1, Michal Mokry1,2,3, Marlot van der Wal1, Rianne Scholman1, Veerle Fleskens4, Aridaman Pandit1, Weiyang Tao1, Mark Wekking3, Stephin Vervoort1,5, Ceri Roberts4, Alessandra Petrelli1, Janneke G C Peeters1, Marthe Knijff1, Sytze de Roock1, Sebastiaan Vastert1, Leonie S Taams4, Jorg van Loosdregt1,5, Femke van Wijk6.
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.Entities:
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Year: 2021 PMID： 33976194 PMCID： PMC8113485 DOI： 10.1038/s41467-021-22975-7
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919