Nuclear orphan receptor NR2F6 directly antagonizes NFAT and RORγt binding to the Il17a promoter
Copyright policy )Nuclear orphan receptor NR2F6 directly antagonizes NFAT and RORγt binding to the Il17a promoter
Interleukin-17A (IL-17A) is the signature cytokine produced by Th17 CD4(+) T cells and has been tightly linked to autoimmune pathogenesis. In particular, the transcription factors NFAT and RORγt are known to activate Il17a transcription, although the detailed mechanism of action remains incompletely understood. Here, we show that the nuclear orphan receptor NR2F6 can attenuate the capacity of NFAT to bind to critical regions of the Il17a gene promoter. In addition, because NR2F6 binds to defined hormone response elements (HREs) within the Il17a locus, it interferes with the ability of RORγt to access the DNA. Consistently, NFAT and RORγt binding within the Il17a locus were enhanced in Nr2f6-deficient CD4(+) Th17 cells but decreased in Nr2f6-overexpressing transgenic CD4(+) Th17 cells. Taken together, our findings uncover an example of antagonistic regulation of Il17a transcription through the direct reciprocal actions of NR2F6 versus NFAT and RORγt.
- Novartis Institutes for BioMedical Research Switzerland
- MEDICEL OY Finland
- MEDIZINISCHE UNIVERSITAT GRAZ Austria
- Novartis (Switzerland) Switzerland
- Innsbruck Medical University Austria
NFAT, Encephalomyelitis, Autoimmune, Experimental, Transcription, Genetic, Immunology, Il17a promoter, Autoimmunity, Response Elements, Binding, Competitive, Article, CD4+ Th17 cells, Mice, Immunology and Allergy, Animals, Mice, Knockout, Binding Sites, NFATC Transcription Factors, Interleukin-17, NR2F6, DNA, Nuclear Receptor Subfamily 1, Group F, Member 3, Mice, Inbred C57BL, Repressor Proteins, Disease Models, Animal, COUP Transcription Factors, Gene Expression Regulation, Th17 Cells, RORγt, Protein Binding, Signal Transduction
NFAT, Encephalomyelitis, Autoimmune, Experimental, Transcription, Genetic, Immunology, Il17a promoter, Autoimmunity, Response Elements, Binding, Competitive, Article, CD4+ Th17 cells, Mice, Immunology and Allergy, Animals, Mice, Knockout, Binding Sites, NFATC Transcription Factors, Interleukin-17, NR2F6, DNA, Nuclear Receptor Subfamily 1, Group F, Member 3, Mice, Inbred C57BL, Repressor Proteins, Disease Models, Animal, COUP Transcription Factors, Gene Expression Regulation, Th17 Cells, RORγt, Protein Binding, Signal Transduction
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).45 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!