CCR5 Directs the Mobilization of CD11b+Gr1+Ly6Clow Polymorphonuclear Myeloid Cells from the Bone Marrow to the Blood to Support Tumor Developmen
CCR5 Directs the Mobilization of CD11b+Gr1+Ly6Clow Polymorphonuclear Myeloid Cells from the Bone Marrow to the Blood to Support Tumor Developmen
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DOI：
10.1016/j.celrep.2017.10.104
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发表时间：
2017-11-21
期刊：
影响因子：
8.8
通讯作者：
Karin, Nathan
中科院分区：
文献类型：
--
作者：
Hawila, Elias;Razon, Hila;Karin, Nathan
造血来源的细胞可细分为淋巴谱系细胞和髓系细胞，其中包括髓源性抑制细胞（MDSC）。MDSC可进一步分为CD 11b（+）Ly 6 G（-）Ly 6C（hi）单核（Mo）MDSC和CD 11b（+）Ly 6 G（+）Ly 6C（low）多形核（PMN）MDSC。这两种亚型都支持肿瘤生长并抑制抗肿瘤免疫。它们在肿瘤部位的积累包括从骨髓动员到血液，然后在肿瘤部位定殖。本研究探讨了PMN-MDSC从BM动员到血液中，然后在肿瘤部位积聚的机制。我们发现趋化因子受体CCR 5是这一事件的关键驱动因素。我们还表明，除了化学吸引力，CCR 5及其配体之间的相互作用促进了骨髓中CCR 5（+）PMN-MDSC的增殖，随后通过诱导β-内酰胺酶-1部分增强了肿瘤部位的免疫抑制活性。
Cells of hematopoietic origin can be subdivided into cells of the lymphoid lineage and those of the myeloid lineage, among which are myeloid-derived suppressor cells (MDSCs). The MDSCs can be further divided into CD11b(+)Ly6G(-)Ly6C(hi) monocytic (Mo) MDSCs and CD11b(+)Ly6G(+)Ly6C (low) polymorphonuclear (PMN) MDSCs. Both subtypes support tumor growth and suppress anti-tumor immunity. Their accumulation at the tumor site includes mobilization from the bone marrow to the blood followed by colonization at the tumor site. The present study examines the mechanism by which PMN-MDSCs are mobilized from the BM to the blood to later accumulate at the tumor site. We show that the chemokine receptor CCR5 is a key driver of this event. We also show that, beyond chemoattraction, the interaction between CCR5 and its ligands promotes the proliferation of CCR5(+) PMN-MDSCs at the BM and, later, potentiates their immune-suppressive activities at the tumor site in part by inducing arginase-1.