title: CD169⁺ macrophages provide a niche promoting erythropoiesis under homeostasis and stress.
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.
authors.affiliation: Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Chow
authors.forename: Matthew
authors.initials: M
authors.lastname: Huggins
authors.forename: Jalal
authors.initials: J
authors.lastname: Ahmed
authors.forename: Daigo
authors.initials: D
authors.lastname: Hashimoto
authors.forename: Daniel
authors.initials: D
authors.lastname: Lucas
authors.forename: Yuya
authors.initials: Y
authors.lastname: Kunisaki
authors.forename: Sandra
authors.initials: S
authors.lastname: Pinho
authors.forename: Marylene
authors.initials: M
authors.lastname: Leboeuf
authors.forename: Clara
authors.initials: C
authors.lastname: Noizat
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Masato
authors.initials: M
authors.lastname: Tanaka
authors.forename: Zhizhuang Joe
authors.initials: ZJ
authors.lastname: Zhao
authors.forename: Aviv
authors.initials: A
authors.lastname: Bergman
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
authors.forename: Paul S
authors.initials: PS
authors.lastname: Frenette
mesh_terms: D000740:Anemia / Q000503:physiopathology; D000743:Anemia, Hemolytic / Q000503:physiopathology; D000818:Animals; D004900:Erythroblasts / Q000502:physiology; D004920:Erythropoiesis / Q000502:physiology*; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011087:Polycythemia Vera / Q000503:physiopathology; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000502:physiology*; D013154:Spleen / Q000502:physiology; D013312:Stress, Physiological / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
chemical_list: D063267:Sialic Acid Binding Ig-like Lectin 1; C571167:Siglec1 protein, mouse; D019010:Vascular Cell Adhesion Molecule-1