Interferon priming is essential for human CD34+ cell-derived plasmacytoid dendritic cell maturation and function
| Autor: | Laustsen, A, Bak, RO, Krapp, C, Kjær, L, Egedahl, JH, Petersen, CC, Pillai, S, Tang, HQ, Uldbjerg, N, Porteus, M, Roan, NR, Nyegaard, M, Denton, PW, Jakobsen, MR |
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| Rok vydání: | 2018 |
| Předmět: |
Cells
1.1 Normal biological development and functioning Antigens CD34 Enzyme-Linked Immunosorbent Assay macromolecular substances Receptor Interferon alpha-beta Regenerative Medicine Polymerase Chain Reaction Interferon alpha-beta Rare Diseases Immunologic Stem Cell Research - Nonembryonic - Human Underpinning research MD Multidisciplinary Receptors Genetics Humans Antigens Cells Cultured Gene Editing Cultured Interleukin-6 Inflammatory and immune system hemic and immune systems Cell Differentiation Dendritic Cells Stem Cell Research Nucleotidyltransferases Toll-Like Receptor 7 Toll-Like Receptor 9 Interferon Type I DEAD Box Protein 58 CD34 CRISPR-Cas Systems Receptor |
| Zdroj: | Nature communications, vol 9, iss 1 Laustsen, A; Bak, RO; Krapp, C; Kjær, L; Egedahl, JH; Petersen, CC; et al.(2018). Interferon priming is essential for human CD34+ cell-derived plasmacytoid dendritic cell maturation and function.. Nature communications, 9(1), 3525. doi: 10.1038/s41467-018-05816-y. UCSF: Retrieved from: http://www.escholarship.org/uc/item/3979k69n |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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