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

Autor: Ceri A. Roberts, Femke van Wijk, Veerle Fleskens, Sytze de Roock, Mark Wekking, Sebastiaan J. Vastert, Marthe Knijff, Gerdien Mijnheer, Weiyang Tao, Janneke G. C. Peeters, Leonie S. Taams, Lisanne Lutter, Michal Mokry, Rianne C. Scholman, Marlot van der Wal, Jorg van Loosdregt, Stephin J. Vervoort, Aridaman Pandit, Alessandra Petrelli
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Cellular differentiation
Cell
General Physics and Astronomy
T-Lymphocytes
Regulatory
Epigenesis
Genetic
Histones
Transcriptome
0302 clinical medicine
BATF
CTLA-4 Antigen
Gene Regulatory Networks
Receptors
Immunologic
Child
Multidisciplinary
Effector
FOXP3
Cell Differentiation
Forkhead Transcription Factors
hemic and immune systems
Cell biology
Basic-Leucine Zipper Transcription Factors
medicine.anatomical_structure
Child
Preschool
Female
Metabolic Networks and Pathways
Adolescent
Science
Primary Cell Culture
chemical and pharmacologic phenomena
Biology
General Biochemistry
Genetics and Molecular Biology
Young Adult
03 medical and health sciences
TIGIT
Glucocorticoid-Induced TNFR-Related Protein
medicine
Humans
Epigenetics
Base Sequence
Gene Expression Profiling
General Chemistry
Arthritis
Juvenile
030104 developmental biology
Case-Control Studies
Receptors
Calcitriol
Joints
Positive Regulatory Domain I-Binding Factor 1
030215 immunology
Zdroj: Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021)
ISSN: 2041-1723
Popis: 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.
Databáze: OpenAIRE
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