Maea expressed by macrophages, but not erythroblasts, maintains postnatal murine bone marrow erythroblastic islands.

The erythroblastic island (EI), formed by a central macrophage and developing erythroblasts (EBs), was first described decades ago and was recently shown to play an in vivo role in homeostatic and pathological erythropoiesis. The exact molecular mechanisms, however, mediating the interactions between macrophages and EBs remain unclear. Macrophage-EB attacher (Maea) has previously been suggested to mediate homophilic adhesion bounds bridging macrophages and EBs. -deficient mice die perinatally with anemia and defective erythrocyte enucleation, suggesting a critical role in fetal erythropoiesis. Here, we generated conditional knockout mouse models of to assess its cellular and postnatal contributions. Deletion of in macrophages using -Cre or -Cre caused severe reductions of bone marrow (BM) macrophages, EBs, and in vivo island formation, whereas its deletion in the erythroid lineage using -Cre had no such phenotype, suggesting a dominant role of Maea in the macrophage for BM erythropoiesis. Interestingly, deletion in spleen macrophages did not alter their numbers or functions. Postnatal deletion using -Cre or function inhibition using a novel monoclonal antibody also impaired BM erythropoiesis. These results indicate that Maea contributes to adult BM erythropoiesis by regulating the maintenance of macrophages and their interaction with EBs via an as-yet-unidentified EB receptor.