Atypical Chemokine Receptor 1 in the Bone Marrow: Implications for Haematopoiesis in African Ancestry
Prof Antal Rot will deliver this talk entitled 'Atypical Chemokine Receptor 1 in the Bone Marrow: Implications for Haematopoiesis in Individuals of African Ancestry'.
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 erythroid cell expression of ACKR1, causing Duffy-negative phenotype. We found an unexpected fundamental role that ACKR1 plays in hematopoiesis which also provides the mechanism linking its absence with neutropenia. Nucleated erythroid cells highly express ACKR1, which facilitates their direct contacts with the hematopoietic stem cells. The absence of erythroid ACKR1 alters murine hematopoiesis, including stem and progenitor cells, ultimately giving rise to phenotypically distinct neutrophils, which leave the circulation, causing neutropenia. Duffy-negative individuals have a distinct profile of neutrophil effector molecules closely reflecting that 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 providing major implications for the selection advantages that have resulted in the paramount fixation of the rs2814778(G) polymorphism in Africa.