Atypical chemokine receptor 1 on nucleated erythroid cells regulates hematopoiesis.
Atypical chemokine receptor 1 on nucleated erythroid cells regulates hematopoiesis.
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DOI：
10.1038/ni.3763
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发表时间：
2017-07
影响因子：
30.5
通讯作者：
Rot A
中科院分区：
文献类型：
--
作者：
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
非洲血统的健康个体患有中性粒细胞减少症，该中性粒细胞减少症与编码非典型趋化因子受体1（ACKR1）的基因的变体rs2814778（G）有关。这种多态性选择性地消除了红系细胞表达的ACKR1，导致达菲阴性表型。在这里，我们描述了一个意想不到的基本作用，ACKR 1在造血中发挥作用，并提供其缺乏与中性粒细胞减少症的机制。有核红系细胞高度表达ACKR 1，这促进了它们与造血干细胞的直接接触。红系ACKR 1的缺乏改变了鼠造血，包括干细胞和祖细胞，最终产生表型不同的中性粒细胞，其容易离开循环，引起中性粒细胞减少症。Duffy阴性个体产生了一种独特的中性粒细胞效应分子谱，这与ACKR 1缺陷小鼠的情况密切相关。因此，造血和骨髓细胞输出的替代生理模式取决于红系细胞中ACKR 1的表达，这为导致rs2814778（G）多态性在非洲最重要的固定的选择优势提供了重要意义。
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. Here we describe an unexpected fundamental role that ACKR1 plays in hematopoiesis and provide the mechanism linking its absence with neutropenia. Nucleated erythroid cells highly expressed ACKR1, which facilitated their direct contacts with the hematopoietic stem cells. The absence of erythroid ACKR1 altered murine hematopoiesis, including stem and progenitor cells, ultimately giving rise to phenotypically distinct neutrophils, which readily left the circulation, causing neutropenia. Duffy-negative individuals developed 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.