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Plasmacytoid dendritic cells (pDC) are essential for immune competence. Here we show that pDC precursor differentiated from human CD34+ hematopoietic stem and progenitor cells (HSPC) has low surface expression of pDC markers, and has limited induction of type I interferon (IFN) and IL-6 upon TLR7 and TLR9 agonists treatment; by contrast, cGAS or RIG-I agonists-mediated activation is not altered. Importantly, after priming with type I and II IFN, these precursor pDCs attain a phenotype and functional activity similar to that of peripheral blood-derived pDCs. Data from CRISPR/Cas9-mediated genome editing of HSPCs further show that HSPC-pDCs with genetic modifications can be obtained, and that expression of the IFN-α receptor is essential for the optimal function, but dispensable for the differentiation, of HSPC-pDC percursor. Our results thus demonstrate the biological effects of IFNs for regulating pDC function, and provide the means of generating of gene-modified human pDCs.
Lausten, A.; Bak, R. O.; Krapp, C.; Kjær, L.; Egedahl, J. H.; Petersen, C. C.; Pillai, S.; Tang, H. Q.; Uldbjerg, N.; Porteus, M.; Roan, N. R.; Nyegaard, M.; Denton, Paul W.; and Jakobsen, M. R., "Interferon priming is essential for human CD34+ cell-derived plasmacytoid dendritic cell maturation and function" (2018). Biology Faculty Publications. 130.
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