RUNX2 Mediates Plasmacytoid Dendritic Cell Egress from the Bone Marrow and Controls Viral Immunity
Plasmacytoid dendritic cells (pDCs) represent a unique immune cell type that responds to viral nucleic acids through the rapid production of type I interferons. Within the hematopoietic system, the transcription factor RUNX2 is exclusively expressed in pDCs and is required for their peripheral homeo...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-04-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716303552 |
| _version_ | 1819040691816235008 |
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| author | Michaël Chopin Simon P. Preston Aaron T.L. Lun Julie Tellier Gordon K. Smyth Marc Pellegrini Gabrielle T. Belz Lynn M. Corcoran Jane E. Visvader Li Wu Stephen L. Nutt |
| author_facet | Michaël Chopin Simon P. Preston Aaron T.L. Lun Julie Tellier Gordon K. Smyth Marc Pellegrini Gabrielle T. Belz Lynn M. Corcoran Jane E. Visvader Li Wu Stephen L. Nutt |
| author_sort | Michaël Chopin |
| collection | DOAJ |
| description | Plasmacytoid dendritic cells (pDCs) represent a unique immune cell type that responds to viral nucleic acids through the rapid production of type I interferons. Within the hematopoietic system, the transcription factor RUNX2 is exclusively expressed in pDCs and is required for their peripheral homeostasis. Here, we show that RUNX2 plays an essential role in promoting pDC localization and function. RUNX2 is required for the appropriate expression of the integrin-mediated adhesion machinery, as well as for the down-modulation of the chemokine receptor CXCR4, which allows pDC egress into the circulation. RUNX2 also facilitates the robust response to viral infection through the control of IRF7, the major regulator of type I interferon production. Mice lacking one copy of Runx2 have reduced numbers of peripheral pDCs and IFN-α expression, which might contribute to the reported difficulties of individuals with cleidocranial dysplasia, who are haploinsufficient for RUNX2, to clear viral infections. |
| first_indexed | 2024-12-21T09:13:08Z |
| format | Article |
| id | doaj.art-a226f734f16d4b40a45e3d4671dfd6c3 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T09:13:08Z |
| publishDate | 2016-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-a226f734f16d4b40a45e3d4671dfd6c32022-12-21T19:09:12ZengElsevierCell Reports2211-12472016-04-0115486687810.1016/j.celrep.2016.03.066RUNX2 Mediates Plasmacytoid Dendritic Cell Egress from the Bone Marrow and Controls Viral ImmunityMichaël Chopin0Simon P. Preston1Aaron T.L. Lun2Julie Tellier3Gordon K. Smyth4Marc Pellegrini5Gabrielle T. Belz6Lynn M. Corcoran7Jane E. Visvader8Li Wu9Stephen L. Nutt10The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaPlasmacytoid dendritic cells (pDCs) represent a unique immune cell type that responds to viral nucleic acids through the rapid production of type I interferons. Within the hematopoietic system, the transcription factor RUNX2 is exclusively expressed in pDCs and is required for their peripheral homeostasis. Here, we show that RUNX2 plays an essential role in promoting pDC localization and function. RUNX2 is required for the appropriate expression of the integrin-mediated adhesion machinery, as well as for the down-modulation of the chemokine receptor CXCR4, which allows pDC egress into the circulation. RUNX2 also facilitates the robust response to viral infection through the control of IRF7, the major regulator of type I interferon production. Mice lacking one copy of Runx2 have reduced numbers of peripheral pDCs and IFN-α expression, which might contribute to the reported difficulties of individuals with cleidocranial dysplasia, who are haploinsufficient for RUNX2, to clear viral infections.http://www.sciencedirect.com/science/article/pii/S2211124716303552 |
| spellingShingle | Michaël Chopin Simon P. Preston Aaron T.L. Lun Julie Tellier Gordon K. Smyth Marc Pellegrini Gabrielle T. Belz Lynn M. Corcoran Jane E. Visvader Li Wu Stephen L. Nutt RUNX2 Mediates Plasmacytoid Dendritic Cell Egress from the Bone Marrow and Controls Viral Immunity Cell Reports |
| title | RUNX2 Mediates Plasmacytoid Dendritic Cell Egress from the Bone Marrow and Controls Viral Immunity |
| title_full | RUNX2 Mediates Plasmacytoid Dendritic Cell Egress from the Bone Marrow and Controls Viral Immunity |
| title_fullStr | RUNX2 Mediates Plasmacytoid Dendritic Cell Egress from the Bone Marrow and Controls Viral Immunity |
| title_full_unstemmed | RUNX2 Mediates Plasmacytoid Dendritic Cell Egress from the Bone Marrow and Controls Viral Immunity |
| title_short | RUNX2 Mediates Plasmacytoid Dendritic Cell Egress from the Bone Marrow and Controls Viral Immunity |
| title_sort | runx2 mediates plasmacytoid dendritic cell egress from the bone marrow and controls viral immunity |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716303552 |
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