Activation of p38 MAPK in CD4 T cells controls IL-17 production and autoimmune encephalomyelitis.
Blood
; 118(12): 3290-300, 2011 Sep 22.
Article
em En
| MEDLINE
| ID: mdl-21791428
ABSTRACT
Although several transcription factors have been shown to be critical for the induction and maintenance of IL-17 expression by CD4 Th cells, less is known about the role of nontranscriptional mechanisms. Here we show that the p38 MAPK signaling pathway is essential for in vitro and in vivo IL-17 production by regulating IL-17 synthesis in CD4 T cells through the activation of the eukaryotic translation initiation factor 4E/MAPK-interacting kinase (eIF-4E/MNK) pathway. We also show that p38 MAPK activation is required for the development and progression of both chronic and relapsing-remitting forms of experimental allergic encephalomyelitis (EAE), the principal autoimmune model of multiple sclerosis. Furthermore, we show that regulation of p38 MAPK activity specifically in T cells is sufficient to modulate EAE severity. Thus, mechanisms other than the regulation of gene expression also contribute to Th17 cell effector functions and, potentially, to the pathogenesis of other Th17 cell-mediated diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
/
Transdução de Sinais
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Autoimunidade
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Interleucina-17
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Fator de Iniciação 4E em Eucariotos
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Proteínas Quinases p38 Ativadas por Mitógeno
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Encefalomielite Autoimune Experimental
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Células Th17
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Blood
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos