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

Qiaozhi Wei, Philip E. Boulais, Dachuan Zhang, Sandra Pinho, Masato Tanaka and Paul S. Frenette

Key points

  • Maea, but not Vcam1, is required for adult bone marrow macrophage development and erythroblastic island function in vivo.

  • Deletion of Maea expressed by macrophages, but not by erythroblasts, impairs bone marrow erythroblastic island formation.

Abstract

The erythroblastic island (EI), formed by a central macrophage and developing erythroblasts, was first described decades ago and recently shown to play an in vivo role in homeostatic and pathological erythropoiesis. The exact molecular mechanisms, however, mediating the interactions between macrophages and erythroblasts remain unclear. Macrophage-Erythroblast Attacher (Maea) has previously been suggested to mediate homophilic adhesion bounds bridging macrophages and erythroblasts. Maea-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 Maea to assess its cellular and postnatal contributions. Deletion of Maea in macrophages using Csf1r-Cre or CD169-Cre caused severe reductions of bone marrow (BM) macrophages, erythroblasts, and in vivo island formation, while its deletion in the erythroid lineage using Epor-Cre had no such phenotype, suggesting a dominant role of Maea in macrophage for BM erythropoiesis. Interestingly, Maea deletion in spleen macrophages did not alter their numbers or functions. Postnatal Maea deletion using Mx1-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 erythroblasts via a yet unidentified erythroblast receptor.

  • Submitted November 26, 2018.
  • Accepted January 18, 2019.