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

Abstract

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 JAK2V617F-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 Users may view, print, copy, download and text and datamine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms Correspondence should be addressed to paul.frenette@einstein.yu.edu or miriam.merad@mssm.edu. *These authors contributed equally to this work. Author Contributions A.C. designed the experiments, conducted experiments, analysed data, and wrote the manuscript. M.M. and P.S.F. designed the experiments and wrote the manuscript. M.H., J.A., D.H., D.L., Y.K., S.P., M.L., and C.N. conducted experiments, analysed data, and provided feedback on the manuscript. N.vR provided clodronate liposomes and feedback on the manuscript. M.T., Z.J.Z. provided mice and feedback on the manuscript. A.B. designed the mathematical model of steady-state erythropoiesis and provided feedback on the manuscript. HHS Public Access Author manuscript Nat Med. Author manuscript; available in PMC 2014 April 11. Published in final edited form as: Nat Med. 2013 April ; 19(4): 429–436. doi:10.1038/nm.3057. A uhor M anscript

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@inproceedings{Chow2013CD169MP, title={CD169+ macrophages provide a niche promoting erythropoiesis under homeostasis, myeloablation and in JAK2V617F-induced polycythemia vera}, author={A. K. K. Chow and Matthew Huggins and Jalal Ahmed and Daigo Hashimoto and Daniel Reed Lucas and Yuya Kunisaki and Sandra Pinho and Maryl{\`e}ne Leboeuf and Clara Noizat and Nico van van Rooijen and Masato Tanaka and Zhizhuang Joe Zhao and Aviv Bergman and Miriam Merad and Paul S Frenette}, year={2013} }