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Nat Immunol. 2014 Feb;15(2):161-7. doi: 10.1038/ni.2795. Epub 2013 Dec 22.

Transcriptional programming of dendritic cells for enhanced MHC class II antigen presentation.

Author information

1
Department of Discovery Immunology, Genentech, South San Francisco, California, USA.
2
Institute for Systems and Genomics Biology and Department of Human Genetics, The University of Chicago, Chicago, Illinois, USA.
3
Department of Bioinformatics and Computational Biology, Genentech, South San Francisco, California, USA.
4
Department of Translational Immunology, Genentech, South San Francisco, California, USA.
5
Department of Research Oncology, Genentech, South San Francisco, California, USA.
6
1] Department of Discovery Immunology, Genentech, South San Francisco, California, USA. [2].

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.

PMID:
24362890
DOI:
10.1038/ni.2795
[Indexed for MEDLINE]

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