Atypical chemokine receptor 1 on nucleated erythroid cells regulates hematopoiesis

Item Type:	Article
Title:	Atypical chemokine receptor 1 on nucleated erythroid cells regulates hematopoiesis
Creators Name:	Duchene, J. and Novitzky-Basso, I. and Thiriot, A. and Casanova-Acebes, M. and Bianchini, M. and Etheridge, S.L. and Hub, E. and Nitz, K. and Artinger, K. and Eller, K. and Caamano, J. and Ruelicke, T. and Moss, P. and Megens, R.T.A. and von Andrian, U.H. and Hidalgo, A. and Weber, C. and Rot, A.
Abstract:	Healthy individuals of African ancestry have neutropenia that has been linked with the variant rs2814778(G) of the gene encoding atypical chemokine receptor 1 (ACKR1). This polymorphism selectively abolishes the expression of ACKR1 in erythroid cells, causing a Duffy-negative phenotype. Here we describe an unexpected fundamental role for ACKR1 in hematopoiesis and provide the mechanism that links its absence with neutropenia. Nucleated erythroid cells had high expression of ACKR1, which facilitated their direct contact with hematopoietic stem cells. The absence of erythroid ACKR1 altered mouse hematopoiesis including stem and progenitor cells, which ultimately gave rise to phenotypically distinct neutrophils that readily left the circulation, causing neutropenia. Individuals with a Duffy-negative phenotype developed a distinct profile of neutrophil effector molecules that closely reflected the one observed in the ACKR1-deficient mice. Thus, alternative physiological patterns of hematopoiesis and bone marrow cell outputs depend on the expression of ACKR1 in the erythroid lineage, findings with major implications for the selection advantages that have resulted in the paramount fixation of the ACKR1 rs2814778(G) polymorphism in Africa.
Keywords:	African Continental Ancestry Group, Bone Marrow, Bone Marrow Cells, Cell Proliferation, Cell Surface Receptors, Chemokine Receptors, Confocal Microscopy, Duffy Blood-Group System, Erythroblasts, Flow Cytometry, Fluorescent Antibody Technique, Hematopoiesis, Hematopoietic Stem Cells, Neutropenia, Neutrophils, Animals, Mice
Source:	Nature Immunology
ISSN:	1529-2908
Publisher:	Nature Publishing Group
Volume:	18
Number:	7
Page Range:	753-761
Date:	July 2017
Official Publication:	https://doi.org/10.1038/ni.3763
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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