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Interferon priming is essential for human CD34+ cell-derived plasmacytoid dendritic cell maturation and function

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...

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Detalles Bibliográficos
Autores principales: Laustsen, 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, P. W., Jakobsen, M. R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117296/
https://www.ncbi.nlm.nih.gov/pubmed/30166549
http://dx.doi.org/10.1038/s41467-018-05816-y
Descripción
Sumario: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.