| First Author | Vander Lugt B | Year | 2014 |
| Journal | Nat Immunol | Volume | 15 |
| Issue | 2 | Pages | 161-7 |
| PubMed ID | 24362890 | Mgi Jnum | J:209280 |
| Mgi Id | MGI:5566918 | Doi | 10.1038/ni.2795 |
| Citation | Vander Lugt B, et al. (2014) Transcriptional programming of dendritic cells for enhanced MHC class II antigen presentation. Nat Immunol 15(2):161-7 |
| abstractText | 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. |
