CD169 + macrophages provide a niche promoting erythropoiesis under homeostasis and stress

Andrew Chow, Matthew Huggins, Jalal Ahmed, Daigo Hashimoto, Daniel Lucas, Yuya Kunisaki, Sandra Pinho, Marylene Leboeuf, Clara Noizat, Nico Van Rooijen, Masato Tanaka, Zhizhuang Joe Zhao, Aviv Bergman, Miriam Merad, Paul S. Frenette

Research output: Contribution to journalArticle

212 Scopus citations

Abstract

A role for macrophages in erythropoiesis was suggested several decades ago when erythroblastic islands in the bone marrow, composed of a central macrophage surrounded by developing erythroblasts, were described. However, the in vivo role of macrophages in erythropoiesis under homeostatic conditions or in disease remains unclear. We found that specific depletion of CD169 + macrophages markedly reduced the number of erythroblasts in the bone marrow but did not result in overt anemia under homeostatic conditions, probably because of concomitant alterations in red blood cell 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 mouse model of polycythemia vera, suggesting that erythropoiesis in polycythemia vera remains under the control of macrophages in the bone marrow and splenic microenvironments. These results indicate that CD169 + macrophages promote late erythroid maturation and that modulation of the macrophage compartment may be a new strategy to treat erythropoietic disorders.

Original languageEnglish (US)
Pages (from-to)429-436
Number of pages8
JournalNature Medicine
Volume19
Issue number4
DOIs
StatePublished - Apr 1 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Chow, A., Huggins, M., Ahmed, J., Hashimoto, D., Lucas, D., Kunisaki, Y., Pinho, S., Leboeuf, M., Noizat, C., Van Rooijen, N., Tanaka, M., Zhao, Z. J., Bergman, A., Merad, M., & Frenette, P. S. (2013). CD169 + macrophages provide a niche promoting erythropoiesis under homeostasis and stress. Nature Medicine, 19(4), 429-436. https://doi.org/10.1038/nm.3057