BioProject

Classical dendritic cells (cDCs) process and present antigens to T cells. Under steady-state conditions, antigen presentation by cDCs induces tolerance. More...

Classical dendritic cells (cDCs) process and present antigens to T cells. Under steady-state conditions, antigen presentation by cDCs induces tolerance. In contrast, during infection or inflammation, cDCs become activated, express higher levels of cell surface MHC molecules, and induce strong adaptive immune responses. We recently identified a cDC-restricted zinc finger transcription factor, zDC, that is not expressed by other immune cell populations, including pDCs, monocytes, or macrophages. Here we define the zDC consensus DNA binding motif and the genes regulated by zDC using chromatin immunoprecipitation and deep sequencing. By deleting zDC from the mouse genome, we show that zDC is primarily a negative regulator of cDC gene expression. zDC deficiency alters the cDC subset composition in the spleen in favor of CD8+ DCs, upregulates activation pathways in steady state cDCs including elevated MHC II expression, and enhances cDC production of VEGF leading to increased vascularization of skin-draining lymph nodes. Consistent with these observations, zDC protein expression is rapidly downregulated after TLR ligation. Thus, zDC is a TLR-responsive cDC-specific transcriptional repressor that is in part responsible for preventing cDC maturation in the steady state. Overall design: Splenic classical dendritic cells from mice lacking the second exon of the zDC gene were sorted. DEC-205+ and DCIR2+ cDCs from the zDC knockout mice were collected for comparison with wildtype cDCs. Three replicates per group. The wildtype samples have been previously analyzed and are available in the GEO database in Series GSE6259. The complete dataset representing: (1) the zDC knockout Samples and (2) the wildtype Samples from Series GSE6259 (re-processed using RMA), is linked below as a supplementary file. Less...