Journal article
RUNX2 Mediates Plasmacytoid Dendritic Cell Egress from the Bone Marrow and Controls Viral Immunity
M Chopin, SP Preston, ATL Lun, J Tellier, GK Smyth, M Pellegrini, GT Belz, LM Corcoran, JE Visvader, L Wu, SL Nutt
Cell Reports | Published : 2016
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, ..
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Awarded by Australian Research Council
Funding Acknowledgements
We thank J. Leahy, E. Lanera, A. D'Amico, T. Kratina, D. Emslie, and the institute flow cytometry facility for technical assistance. This work was supported by grants (1048278, 1023266, 1045549, 361646, 1065626, and 1016701) and fellowships (to L.W., G.T.B., and S.L.N.) from the National Health and Medical Research Council (NHMRC) of Australia. S.L.N. and G.T.B were supported by an Australian Research Council Future Fellowship, J.E.V. was supported by an Australia Fellowship, M.P. held a Viertel Fellowship, and L.W. was supported by a Key Project Grant from the Natural Science Foundation of China (31330027). This work was made possible through Victorian State Government Operational Infrastructure Support and the NHMRC IRIIS.