DNGR-1 regulates proliferation and migration of bone marrow dendritic cell progenitors

Conventional dendritic cells (cDCs) are sentinel cells that play a crucial role in both innate and adaptive immune responses. cDCs originate from a common progenitor (pre-cDC) in the bone marrow (BM) that travels via the blood to seed peripheral tissues before locally differentiating into functional cDC1 and cDC2 cells, a process known as cDCpoiesis. We show that DNGR-1, an innate immune receptor expressed by cDC progenitors and type 1 cDCs, functionally regulates cDCpoiesis in mice. In a competitive chimera setting, cDC progenitors lacking DNGR-1 exhibit increased proliferation and tissue migratory potential. Compared to their wildtype counterparts, DNGR-1-deficient cDC progenitor cells display superior colonization of peripheral tissues but an altered distribution. These findings suggest that cDCpoiesis can be regulated in part by cell-intrinsic processes driven by signals from innate immune receptors such as DNGR-1 that may respond to alterations in the BM milieu Transcriptome analysis was performed in bone marrow and spleen pre-cDCs population from DNGR1 KO CD42.2 and BL/6 CD45.1 mice (bone marrow chimeras)