Dendritic cells (DCs) have evolved into a highly diverse family of cellular subsets, each with their own distinctive functional features. Plasmacytoid DCs (pDCs) represent a unique immune cell type which responds to viral nucleic acids through the rapid production of type-I interferons. The molecular cues driving the of this peculiar DC subset remains to be fully uncovered. In a genomic screen aiming to unravel the molecular network underpinning DC diversity, we identified the transcription factor RUNX2 as being exclusively expressed in pDC.
To explore its role in pDC ontogeny/function we developed a conditional mutation that allows inactivation of Runx2 in adult hematopoietic cells. Runx2 deletion does not impair the development of pDC in in the bone marrow, but greatly impairs their homing capacity to the secondary lymphoid organs. Phenotypic analysis reveals that Runx2-/- pDC have disturbed expression of specific constituents of integrin-mediated adhesion machinery, preventing their adherence to extracellular matrix, a property which is essential for pDC transmigration into the blood circulation. This lack of peripheral pDC renders Runx2-/- mice unable to mount an innate antiviral immune response to acute Lymphocytic Choriomeningitis virus (LCMV). Moreover RUNX2 haploinsufficient mice show a reduced number of peripheral DC, which might explain the failure of Cleidocranial Dysplasia (CCD) human patients that are haploinsufficent for RUNX2, to clear viral infections.
Taken together, our results revealed the specific expression of a novel transcription factor in pDCs, which is essential for their homeostasis, and might shed light on the immune condition harbored by CCD patients.