ACKR2 in hematopoietic precursors as a checkpoint of neutrophil release and anti-metastatic activity.
ACKR2 in hematopoietic precursors as a checkpoint of neutrophil release and anti-metastatic activity.
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DOI：
10.1038/s41467-018-03080-8
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发表时间：
2018-02-14
影响因子：
16.6
通讯作者：
Bonecchi R
中科院分区：
文献类型：
--
作者：
Massara M;Bonavita O;Savino B;Caronni N;Mollica Poeta V;Sironi M;Setten E;Recordati C;Crisafulli L;Ficara F;Mantovani A;Locati M;Bonecchi R
非典型趋化因子受体（ACKR）是白细胞运输、炎症和免疫的调节剂。ACKR 2是大多数炎性CC趋化因子的清除剂，并且是炎症的负调节剂。在这里，我们报告说，ACKR2在造血前体细胞中表达，并在骨髓分化过程中下调。ACKR 2的基因失活导致炎性趋化因子受体水平增加，并导致中性粒细胞从骨髓中释放，抗转移活性增加。在NeuT驱动的原发性乳腺癌发生模型中，ACKR2缺陷与原发性肿瘤生长增加和防止转移相关。在原位移植4T1乳腺癌并静脉注射B16 F10黑色素瘤细胞系的小鼠中，ACKR 2缺陷导致嗜酸性粒细胞介导的抗转移保护。因此，ACKR2是小鼠骨髓分化和功能的关键调节因子（检查点），并且其靶向释放小鼠中嗜中性粒细胞的抗转移活性。非典型趋化因子受体ACKR2调节免疫反应。在本文中，作者证实了ACKR2耗竭促进原发性肿瘤生长，但通过影响骨髓分化和释放中性粒细胞的抗转移活性，在乳腺癌小鼠模型中显示出抗转移作用。
Atypical chemokine receptors (ACKRs) are regulators of leukocyte traffic, inflammation, and immunity. ACKR2 is a scavenger for most inflammatory CC chemokines and is a negative regulator of inflammation. Here we report that ACKR2 is expressed in hematopoietic precursors and downregulated during myeloid differentiation. Genetic inactivation of ACKR2 results in increased levels of inflammatory chemokine receptors and release from the bone marrow of neutrophils with increased anti-metastatic activity. In a model of NeuT-driven primary mammary carcinogenesis ACKR2 deficiency is associated with increased primary tumor growth and protection against metastasis. ACKR2 deficiency results in neutrophil-mediated protection against metastasis in mice orthotopically transplanted with 4T1 mammary carcinoma and intravenously injected with B16F10 melanoma cell lines. Thus, ACKR2 is a key regulator (checkpoint) of mouse myeloid differentiation and function and its targeting unleashes the anti-metastatic activity of neutrophils in mice. The atypical chemokine receptor ACKR2 regulates immune responses. Here the authors confirm that ACKR2 depletion promotes primary tumor growth but show it has an anti-metastatic effect in mouse models of breast cancer by affecting myeloid differentiation and unleashing the anti-metastatic activity of neutrophils.
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DOI：
10.1084/jem.20092210
发表时间：
2010-05-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Allende ML;Tuymetova G;Lee BG;Bonifacino E;Wu YP;Proia RL
通讯作者：
Proia RL
影响因子：
2.1
作者：
Baba T;Mukaida N
通讯作者：
Mukaida N
影响因子：
7.3
作者：
Bonecchi R;Graham GJ
通讯作者：
Graham GJ
影响因子：
50.3
作者：
Granot Z;Henke E;Comen EA;King TA;Norton L;Benezra R
通讯作者：
Benezra R
影响因子：
20.3
作者：
Bonecchi, Raffaella;Borroni, Elena M.;Locati, Massimo
通讯作者：
Locati, Massimo