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Dual role for atypical chemokine receptor 1 in myeloid cell hematopoiesis and distribution

Cellular & Molecular Immunology volume 15, pages 399–401 (2018)Cite this article

Similar to conventional chemokine receptors, atypical chemokine receptors (ACKRs) are cell-surface receptors that possess a seven transmembrane domain structure and regulate immune responses by interacting with chemokines. However, ACKRs differ from conventional chemokine receptors because of their inability to couple to G proteins and therefore to transduce intracellular signals mediating leukocyte migration upon chemokine binding. Instead, ACKRs internalize, transport or scavenge chemokines, regulating their extracellular availability, and thus impacting homeostasis, inflammation and immune response.1,2,3

ACKR1, also known as Duffy antigen receptor for chemokines, is expressed in endothelial cells (ECs), erythrocytes and a subset of neurons.4 On ECs, ACKR1 regulates inflammatory responses by transporting chemokines to the luminal surface of vessels, presenting them to rolling leukocytes.5 In the brain, ACKR1 regulates neurotransmission and the activity of Purkinje neurons, influencing motor function and behavior.6 In erythrocytes, ACKR1 is believed to function as a blood-based chemokine buffer by taking up, accumulating and degrading chemokines.7 Moreover, ACKR1 expressed on erythrocytes provides binding sites for Plasmodium vivax and Plasmodium knowlesi, enhancing susceptibility to malaria.8 Interestingly, most individuals in Sub-Saharan Africa bear a single-nucleotide polymorphism in the ACKR1 promoter that disrupts the binding site for the transcription factor GATA-1, and thus impairs the expression of ACKR1 in erythrocytes but not in ECs.9,10 Due to the associated resistance to malaria, this ‘Duffy-negative phenotype’ has conferred an evolutionary advantage and is widespread in African diaspora. These individuals have low neutrophil cell counts, or neutropenia, which mechanism so far has remained unresolved.11

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Acknowledgements

The work of RF is supported by the grants of the Deutsche Forschungsgemeinschaft (SFB900-B1, SFB738-B5, KFO250, FO334/5-1), the European Research Council (ERC Advanced Grant 322645), and the Government of Lower Saxony (N-RENNT, BioFabrication for NIFE).

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  1. These authors contributed equally to this work.

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  1. Institute of Immunology, Hannover Medical School, Carl-Neuberg-Straβe 1, 30625, Hannover, Germany

    Marc Permanyer, Berislav Bošnjak & Reinhold Förster

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Correspondence to Reinhold Förster.

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Permanyer, M., Bošnjak, B. & Förster, R. Dual role for atypical chemokine receptor 1 in myeloid cell hematopoiesis and distribution. Cell Mol Immunol 15, 399–401 (2018). https://doi.org/10.1038/cmi.2017.79

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