1. Atypical chemokine receptor 1 on nucleated erythroid cells regulates hematopoiesis
- Author
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S. Leah Etheridge, Maria Casanova-Acebes, Johan Duchene, Jorge Caamano, Christian Weber, Mariaelvy Bianchini, Igor Novitzky-Basso, Remco T. A. Megens, Kathrin Eller, Elin Hub, Katharina Artinger, Antal Rot, Thomas Rülicke, Paul Moss, Katrin Nitz, Andrés Hidalgo, Ulrich H. von Andrian, Aude Thiriot, Biochemie, and RS: CARIM - R3.07 - Structure-function analysis of the chemokine interactome for therapeutic targeting and imaging in atherosclerosis
- Subjects
0301 basic medicine ,Chemokine ,Erythroblasts ,Neutrophils ,Fluorescent Antibody Technique ,Stem cell factor ,Mice ,Chemokine receptor ,Bone Marrow ,BLOOD-GROUP ,Immunology and Allergy ,Microscopy, Confocal ,biology ,Flow Cytometry ,Research Highlight ,Phenotype ,PLASMODIUM-VIVAX ,Cell biology ,Haematopoiesis ,medicine.anatomical_structure ,Receptors, Chemokine ,Stem cell ,STEM-CELLS ,Neutropenia ,BONE-MARROW ,Immunology ,DARC ,Black People ,Bone Marrow Cells ,Receptors, Cell Surface ,DUFFY ANTIGEN RECEPTOR ,Article ,INFLAMMATORY CHEMOKINES ,03 medical and health sciences ,HOST-DEFENSE ,Erythroid Cells ,NEGATIVE INDIVIDUALS ,medicine ,Animals ,Humans ,Progenitor cell ,Cell Proliferation ,Hematopoietic Stem Cells ,ENDOTHELIAL-CELLS ,Hematopoiesis ,030104 developmental biology ,biology.protein ,Bone marrow ,Duffy Blood-Group System - 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.
- Published
- 2017