Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response.
Science
; 324(5932): 1334-8, 2009 Jun 05.
Article
em En
| MEDLINE
| ID: mdl-19498172
ABSTRACT
A central challenge for improving autoimmune therapy is preventing inflammatory pathology without inducing generalized immunosuppression. T helper 17 (TH17) cells, characterized by their production of interleukin-17, have emerged as important and broad mediators of autoimmunity. Here we show that the small molecule halofuginone (HF) selectively inhibits mouse and human TH17 differentiation by activating a cytoprotective signaling pathway, the amino acid starvation response (AAR). Inhibition of TH17 differentiation by HF is rescued by the addition of excess amino acids and is mimicked by AAR activation after selective amino acid depletion. HF also induces the AAR in vivo and protects mice from TH17-associated experimental autoimmune encephalomyelitis. These results indicate that the AAR pathway is a potent and selective regulator of inflammatory T cell differentiation in vivo.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Subpopulações de Linfócitos T
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Linfócitos T Auxiliares-Indutores
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Quinazolinonas
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Aminoácidos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos