RUNX2 mediates plasmacytoid dendritic cell egress from the bone marrow and controls viral immunity
Details
Publication Year 2016-04-13, Volume 15, Issue #4, Page 866-878
Journal Title
Cell Rep
Publication Type
Journal Article
Abstract
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-alpha expression, which might contribute to the reported difficulties of individuals with cleidocranial dysplasia, who are haploinsufficient for RUNX2, to clear viral infections.
Publisher
Cell Press
WEHI Research Division(s)
Molecular Immunology; Infection And Immunity; Bioinformatics; Stem Cells And Cancer
PubMed ID
27149837
Open Access at Publisher's Site
https://doi.org/10.1016/j.celrep.2016.03.066
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2016-06-17 03:01:34
Last Modified: 2018-07-09 03:13:29
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