Nuclear orphan receptor NR2F6 directly antagonizes NFAT and RORγt binding to the Il17a promoter.
J Autoimmun
; 39(4): 428-40, 2012 Dec.
Article
en En
| MEDLINE
| ID: mdl-22921335
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Interleucina-17
/
Encefalomielitis Autoinmune Experimental
/
Factores de Transcripción COUP
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Factores de Transcripción NFATC
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Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares
/
Células Th17
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Autoimmun
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Austria