Bhlhe40 controls cytokine production by T cells and is essential for pathogenicity in autoimmune neuroinflammation.
Nat Commun
; 5: 3551, 2014 Apr 03.
Article
em En
| MEDLINE
| ID: mdl-24699451
ABSTRACT
TH1 and TH17 cells mediate neuroinflammation in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Pathogenic TH cells in EAE must produce the pro-inflammatory cytokine granulocyte-macrophage colony stimulating factor (GM-CSF). TH cell pathogenicity in EAE is also regulated by cell-intrinsic production of the immunosuppressive cytokine interleukin 10 (IL-10). Here we demonstrate that mice deficient for the basic helix-loop-helix (bHLH) transcription factor Bhlhe40 (Bhlhe40(-/-)) are resistant to the induction of EAE. Bhlhe40 is required in vivo in a T cell-intrinsic manner, where it positively regulates the production of GM-CSF and negatively regulates the production of IL-10. In vitro, GM-CSF secretion is selectively abrogated in polarized Bhlhe40(-/-) TH1 and TH17 cells, and these cells show increased production of IL-10. Blockade of IL-10 receptor in Bhlhe40(-/-) mice renders them susceptible to EAE. These findings identify Bhlhe40 as a critical regulator of autoreactive T-cell pathogenicity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fator Estimulador de Colônias de Granulócitos e Macrófagos
/
Interleucina-10
/
Proteínas de Homeodomínio
/
Encefalomielite Autoimune Experimental
/
Fatores de Transcrição Hélice-Alça-Hélice Básicos
/
Esclerose Múltipla
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos