Transcriptional programming of dendritic cells for enhanced MHC class II antigen presentation.
Nat Immunol
; 15(2): 161-7, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24362890
ABSTRACT
CD11b(+) dendritic cells (DCs) seem to be specialized for presenting antigens via major histocompatibility (MHC) class II complexes to stimulate helper T cells, but the genetic and regulatory basis for this is not established. Conditional deletion of Irf4 resulted in loss of CD11b(+) DCs, impaired formation of peptide-MHC class II complexes and defective priming of helper T cells but not of cytotoxic T lymphocyte (CTL) responses. Gene expression and chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) analyses delineated an IRF4-dependent regulatory module that programs enhanced MHC class II antigen presentation. Expression of the transcription factor IRF4 but not of IRF8 restored the ability of IRF4-deficient DCs to efficiently process and present antigen to MHC class II-restricted T cells and promote helper T cell responses. We propose that the evolutionary divergence of IRF4 and IRF8 facilitated the specialization of DC subsets for distinct modes of antigen presentation and priming of helper T cell versus CTL responses.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Linfócitos T Citotóxicos
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Antígenos de Histocompatibilidade Classe II
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Linfócitos T Auxiliares-Indutores
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Apresentação de Antígeno
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Fatores Reguladores de Interferon
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article