IFN-ß Selectively Inhibits IL-2 Production through CREM-Mediated Chromatin Remodeling.
J Immunol
; 194(11): 5120-8, 2015 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-25888642
ABSTRACT
IFN-ß is widely used in the treatment of multiple sclerosis, yet the mechanism facilitating its efficacy remains unclear. IL-2 production by activated T cells, including those mediating autoimmunity, and subsequent autocrine stimulation is vital for T cell expansion and function. In this study, we demonstrate that in mouse and human T cells, IFN-ß specifically inhibits the production of IL-2 upon TCR engagement without affecting other cytokines or activation markers. Rather than disrupting TCR signaling, IFN-ß alters histone modifications in the IL-2 promoter to retain the locus in an inaccessible configuration. This in turn is mediated through the upregulation of the transcriptional suppressor CREM by IFN-ß and consequent recruitment of histone deacetylases to the IL-2 promoter. In accordance, ablation of CREM expression or inhibition of histone deacetylases activity eliminates the suppressive effects of IFN-ß on IL-2 production. Collectively, these findings provide a molecular basis by which IFN-ß limits T cell responses.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Interleucina-2
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Interferón beta
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Linfocitos T Reguladores
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Ensamble y Desensamble de Cromatina
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Modulador del Elemento de Respuesta al AMP Cíclico
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Año:
2015
Tipo del documento:
Article