Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Duchene, J; Novitzky-Basso, I; Thiriot, A; Casanova-Acebes, M; Bianchini, M; Etheridge, SL; Hub, E; Nitz, K; Artinger, K; Eller, K; Caamaño, J; Rülicke, T; Moss, P; Megens, RTA; von Andrian, UH; Hidalgo, A; Weber, C; Rot, A.
Atypical chemokine receptor 1 on nucleated erythroid cells regulates hematopoiesis.
Nat Immunol. 2017; 18(7):753-761
Doi: 10.1038/ni.3763
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- Co-Autor*innen der Med Uni Graz
- Artinger Katharina
- Eller Kathrin
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- African Continental Ancestry Group - genetics
- Animals -
- Bone Marrow - pathology
- Bone Marrow Cells - metabolism
- Cell Proliferation -
- Duffy Blood-Group System - genetics
- Duffy Blood-Group System - metabolism
- Erythroblasts - metabolism
- Flow Cytometry -
- Fluorescent Antibody Technique -
- Hematopoiesis - genetics
- Hematopoietic Stem Cells - cytology
- Hematopoietic Stem Cells - metabolism
- Humans -
- Mice -
- Microscopy, Confocal -
- Neutropenia - genetics
- Neutrophils - cytology
- Neutrophils - metabolism
- Receptors, Cell Surface - genetics
- Receptors, Cell Surface - metabolism
- Receptors, Chemokine - genetics
- Receptors, Chemokine - metabolism