Abstract
DCs express receptors sensing microbial, danger or cytokine signals, which when triggered in combination drive DC maturation and functional polarization. Maturation was proposed to result from a discrete number of modifications in conventional DCs (cDCs), in contrast to a cell-fate conversion in plasmacytoid DCs (pDCs). cDC maturation is generally assessed by measuring cytokine production and membrane expression of MHC class II and co-stimulation molecules. pDC maturation complexity was demonstrated by functional genomics. Here, pDCs and cDCs were shown to undergo profound and convergent changes in their gene expression programs in vivo during viral infection. This observation was generalized to other stimulation conditions and DC subsets, by public microarray data analyses, PCR confirmation of selected gene expression profiles, and gene regulatory sequence bioinformatics analyses. Thus, maturation is a complex process similarly reshaping all DC subsets, including through the induction of a core set of NF-κB- or IFN-stimulated genes irrespective of stimuli.
Highlights
DCs are specialized in the processing of peptide antigens and their presentation in association with MHC molecules for the activation of naıve T lymphocytes [1]
For the first time to the best of our knowledge, we established that the maturation of spleen-resident DC subsets during a viral infection arose from widespread common changes in their gene expression programs in plasmacytoid DCs (pDCs) and in CD8α+ and CD11b+ conventional DCs (cDCs) which were much more profoundly reshaped than anticipated
Many of the genes expressed in q pDCs as compared with many other leukocyte types were still expressed to much higher levels in a pDCs than in a cDCs, even if they were decreased as compared with those in q pDCs, including the genes coding for the transcription factors E2–2 and Runx2 and for the www.eji-journal.eu were enriched for putative transcription factor binding sites for ISGF3, IRFs, and NF-κB
Summary
DCs are specialized in the processing of peptide antigens and their presentation in association with MHC molecules for the activation of naıve T lymphocytes [1]. DCs express many innate immune recognition receptors that allow them to sense and integrate microbial, danger, or cytokine signals early during infection or tumorigenesis. During this activation process, DCs undergo morphological, phenotypical, and functional changes that are globally referred to as maturation [2]. Mature DCs deliver three kinds of output signals to T cells: (i) cognate engagement of the TCR by MHC+peptide complexes, (ii) engagement of coreceptors by co-stimulation molecules, and (iii) cytokines. Different input signals received by DCs determine the delivery of distinct output signals to T cells which determine their functional polarization [2]
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