Transcription factor Runx2 controls the development and migration of plasmacytoid dendritic cells
| Autor: | Hiyaa S. Ghosh, Louis M. Staudt, Catherine M. Sawai, Michele Ceribelli, Esther Z. Hou, Vanja Sisirak, Boris Reizis |
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| Přispěvatelé: | Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, Lymphoid Malignancy Branch, Center for Cancer Research, National Cancer Institute, Rockville, MD 20852 |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
CCR2
Cellular differentiation [SDV]Life Sciences [q-bio] Core Binding Factor Alpha 1 Subunit Mice Chemokine receptor 0302 clinical medicine Cell Movement Interferon shRNA Immunology and Allergy cDC Mice Knockout Dox 0303 health sciences musculoskeletal neural and ocular physiology Cell Differentiation hemic and immune systems musculoskeletal system Cell biology RUNX2 medicine.anatomical_structure embryonic structures Transcription Factor 7-Like 2 Protein NK Cell Lectin-Like Receptor Subfamily A medicine.drug musculoskeletal diseases Receptors CCR5 Immunology ChIP Bone Marrow Cells chromatin immunoprecipitation Biology 03 medical and health sciences Immune system stomatognathic system plasmacytoid DC medicine Animals Humans short hairpin RNA Transcription factor 030304 developmental biology doxycycline pDC Brief Definitive Report Dendritic Cells classical DC Mice Inbred C57BL Gene Expression Regulation Bone marrow Gene Deletion Transcription Factors 030215 immunology |
| Zdroj: | Journal of Experimental Medicine Journal of Experimental Medicine, Rockefeller University Press, 2020, 210, pp.2151-2159. ⟨10.1084/jem.20130443⟩ The Journal of Experimental Medicine |
| ISSN: | 0022-1007 1540-9538 |
| DOI: | 10.1084/jem.20130443⟩ |
| Popis: | Exit of mature pDCs from the bone marrow requires the transcription factor Runx2, in part via Runx2-driven expression of CCR5. Plasmacytoid dendritic cells (pDCs) rapidly produce type I interferon (IFN-I) in response to viruses and are essential for antiviral immune responses. Although related to classical DCs (cDCs) in their development and expression profile, pDCs possess many distinct features. Unlike cDCs, pDCs develop in the bone marrow (BM) and emerge into peripheral lymphoid organs and tissues as fully differentiated cells. We now report that pDCs specifically express Runx2, a Runt family transcription factor that is essential for bone development. pDCs in Runx2-deficient mice developed normally in the BM but were greatly reduced in the periphery. The defect was cell-intrinsic and was associated with the retention of mature Ly49Q+ pDCs in the BM. Runx2 was required for the expression of several pDC-enriched genes, including the chemokine receptors Ccr2 and Ccr5. Mature pDCs expressed high levels of Ccr5 at the cell surface, and Ccr5-deficient pDCs in a competitive setting were reduced in the periphery relative to the BM. Thus, Runx2 is required for the emergence of mature BM pDCs into the periphery, in a process that is partially dependent on Ccr5. These results establish Runx2 as a lineage-specific regulator of immune system development. |
| Databáze: | OpenAIRE |
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