Myeloid Dendritic Cells Regulate HSPC Trafficking In The Bone Marrow

Granulocyte-colony stimulating factor (G-CSF) is the prototypic agent used to mobilize hematopoietic stem and progenitor cells (HSPCs) into the blood where they can then be harvested for stem cell transplantation. G-CSF acts in a non-cell-intrinsic fashion to induce HSPC mobilization. We recently showed that G-CSF signaling in a CD68+ monocyte/macrophage lineage cell within the bone marrow initiates the HSPC mobilization cascade (Christopher et al., 2011). CD68 marks a heterogeneous cell population that includes monocytes, macrophages, myeloid dendritic cells, and osteoclasts. Within the bone marrow, myeloid dendritic cells (MDCs) are found perivascularly and in close association with CXCL12-abundant reticular (CAR) cells, suggesting a role for MDCs in maintaining HSPC niche function. We previously reported that G-CSF treatment (250 µg/kg per day for 5 days) suppresses macrophage (11.8 ± 3.6-fold) and myeloid dendritic cell (MDCs; 5.5 ± 1.2-fold) numbers in the bone marrow (Supakorndej et al., ASH abstract #2319, 2012). Moreover, we showed that CD11c-DTR mediated MDC ablation results in a modest mobilization of HSPCs. However, CD11c-DTR ablates bone marrow macrophages, as well as MDCs, so a definitive role for MDCs in G-CSF-induced HSPC mobilization could not be established.