Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation
Publication date
2021-12
Authors
Mijnheer, Gerdien
Lutter, Lisanne
Mokry, Michal
van der Wal, M Marlot
Scholman, Rianne C.
Fleskens, Veerle
Pandit, Aridaman
Tao, Weiyang
Wekking, Mark
Vervoort, Stephin
Editors
Advisors
Supervisors
Document Type
Article
Metadata
Show full item recordCollections
License
cc_by
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.
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, General Chemistry, General Biochemistry,Genetics and Molecular Biology, General Physics and Astronomy, Journal Article, Research Support, Non-U.S. Gov't
Citation
Mijnheer, G, Lutter, L, Mokry, M, van der Wal, M, Scholman, R, Fleskens, V, Pandit, A, Tao, W, Wekking, M, Vervoort, S, Roberts, C, Petrelli, A, Peeters, J G C, Knijff, M, de Roock, S, Vastert, S, Taams, L S, van Loosdregt, J & van Wijk, F 2021, 'Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation', Nature Communications, vol. 12, no. 1, 2710, pp. 1-16. https://doi.org/10.1038/s41467-021-22975-7