The nuclear receptor REV-ERBα modulates Th17 cell-mediated autoimmune disease.
Proc Natl Acad Sci U S A
; 116(37): 18528-18536, 2019 09 10.
Article
en En
| MEDLINE
| ID: mdl-31455731
ABSTRACT
T helper 17 (Th17) cells produce interleukin-17 (IL-17) cytokines and drive inflammatory responses in autoimmune diseases such as multiple sclerosis. The differentiation of Th17 cells is dependent on the retinoic acid receptor-related orphan nuclear receptor RORγt. Here, we identify REV-ERBα (encoded by Nr1d1), a member of the nuclear hormone receptor family, as a transcriptional repressor that antagonizes RORγt function in Th17 cells. REV-ERBα binds to ROR response elements (RORE) in Th17 cells and inhibits the expression of RORγt-dependent genes including Il17a and Il17f Furthermore, elevated REV-ERBα expression or treatment with a synthetic REV-ERB agonist significantly delays the onset and impedes the progression of experimental autoimmune encephalomyelitis (EAE). These results suggest that modulating REV-ERBα activity may be used to manipulate Th17 cells in autoimmune diseases.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Encefalomielitis Autoinmune Experimental
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Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares
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Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares
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Células Th17
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Esclerosis Múltiple
Límite:
Animals
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Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2019
Tipo del documento:
Article