CD169(+) macrophages provide a niche promoting erythropoiesis under homeostasis, myeloablation and in JAK2V617F-induced polycythemia vera

The role of macrophages in erythropoiesis was suggested several decades ago with the description of “erythroblastic islands” in the bone marrow (BM) composed of a central macrophage surrounded by developing erythroblasts. However, the in vivo role of macrophages in erythropoiesis under homeostasis or disease remains unclear. Specific depletion of CD169(+) macrophages markedly reduced erythroblasts in the BM but did not result in overt anemia under homeostasis likely due to concomitant alterations in RBC clearance. However, CD169(+) macrophage depletion significantly impaired erythropoietic recovery from hemolytic anemia, acute blood loss and myeloablation. Furthermore, macrophage depletion normalized the erythroid compartment in a JAK2(V617F)-driven murine model of polycythemia vera (PV), suggesting that erythropoiesis in PV, unexpectedly, remains under the control of macrophages in the BM and splenic microenvironments. These data indicate that CD169(+) macrophages promote late erythroid maturation and that modulation of the macrophage compartment represents a novel strategy to treat erythropoietic disorders.