Bone marrow dendritic cells regulate hematopoietic stem/progenitor cell trafficking

A resident population of dendritic cells (DCs) has been identified in murine bone marrow, but its contribution to the regulation of hematopoiesis and establishment of the stem cell niche is largely unknown. Here, we show that murine bone marrow DCs are perivascular and have a type 2 conventional DC (cDC2) immunophenotype. RNA expression analysis of sorted bone marrow DCs shows that expression of many chemokines and chemokine receptors is distinct from that observed in splenic cDC2s, suggesting that bone marrow DCs may represent a unique DC population. A similar population of DCs is present in human bone marrow. Ablation of conventional DCs (cDCs) results in hematopoietic stem/progenitor cell (HSPC) mobilization that is greater than that seen with ablation of bone marrow macrophages, and cDC ablation also synergizes with G-CSF to mobilize HSPCs. Ablation of cDCs is associated with an expansion of bone marrow endothelial cells and increased vascular permeability. CXCR2 expression in sinusoidal endothelial cells and the expression of two CXCR2 ligands, CXCL1 and CXCL2, in the bone marrow are markedly increased following cDC ablation. Treatment of endothelial cells in vitro with CXCL1 induces increased vascular permeability and HSPC transmigration. Finally, we show that HSPC mobilization after cDC ablation is attenuated in mice lacking CXCR2 expression. Collectively, these data suggest that bone marrow DCs play an important role in regulating HSPC trafficking, in part, through regulation of sinusoidal CXCR2 signaling and vascular permeability.