Metallothioneins negatively regulate IL-27-induced type 1 regulatory T-cell differentiation.
Proc Natl Acad Sci U S A
; 110(19): 7802-7, 2013 May 07.
Article
em En
| MEDLINE
| ID: mdl-23630250
ABSTRACT
IL-27-induced type 1 regulatory T (Tr1) cells suppress autoimmunity by producing IL-10. Signal transducer and activator of transcription (STAT) 1 and STAT3 have been described as key transcription factors that promote IL-10 secretion from Tr1 cells induced by IL-27. However, the molecular pathways for negatively regulating Tr1 cell differentiation remain elusive. Here, we show that IL-27 induces metallothioneins (MTs) that in turn prevent Tr1 cell development. MT expression leads to the reduction of STAT1 and STAT3 phosphorylation under Tr1 differentiation condition, resulting in impaired IL-10 production. Accordingly, Tr1 cells derived from MT-deficient mice showed an increased ability to produce IL-10 and potently suppress experimental autoimmune encephalomyelitis upon adoptive transfer. Moreover, activation of STAT1 and/or STAT3 can overcome the suppression of IL-10 by MTs, indicating a dynamic balance between STATs and MTs in regulating IL-10 during Tr1 cell differentiation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
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Regulação da Expressão Gênica
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Linfócitos T Reguladores
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Interleucina-17
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Metalotioneína
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article