CCRL2 is a nonsignaling seven-transmembrane domain receptor. CCRL2 binds chemerin, a protein that promotes chemotaxis of leukocytes, including macrophages and natural killer (NK) cells. In addition, CCRL2 controls the inflammatory response in different pathologic settings, such as hypersensitivity, inflammatory arthritis, and experimental autoimmune encephalitis. Here, we investigated the role of CCRL2 in the regulation of lung cancer-related inflammation. The genetic deletion of Ccrl2 promoted tumor progression in urethane-induced and in Kras G12D/+/p53 LoxP lung tumor mouse models. Similarly, a Kras-mutant lung tumor displayed enhanced growth in Ccrl2-deficient mice. This phenotype was associated with a reduced inflammatory infiltrate characterized by the impaired recruitment of several leukocyte populations including NK cells. Bone marrow chimeras showed that CCRL2 expression by the nonhematopoietic cell compartment was responsible for the increased tumor formation observed in Kras-mutant Ccrl2-deficient mice. In human and mouse lungs, CCRL2 was expressed by a fraction of CD31+ endothelial cells, where it could control NK infiltration. Elevated CCRL2 expression in biopsies from human lung adenocarcinoma positively correlated with clinical outcome. These results provide evidence for a crucial role of CCRL2 in shaping an anti-lung tumor immune response.

中文翻译：

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非典型受体CCRL2对于肺癌免疫监测至关重要。

CCRL2是无信号的七跨膜结构域受体。CCRL2结合凯莫瑞（chemerin），凯莫瑞是一种促进白细胞，包括巨噬细胞和自然杀伤（NK）细胞趋化性的蛋白质。另外，CCRL2在不同的病理环境中控制炎症反应，例如超敏反应，炎症性关节炎和实验性自身免疫性脑炎。在这里，我们调查了CCRL2在调节肺癌相关炎症中的作用。Ccrl2的基因删除促进尿烷诱导的和Kras G12D / + / p53 LoxP肺肿瘤小鼠模型中的肿瘤进展。同样，在Ccrl2缺陷型小鼠中，Kras突变型肺肿瘤显示出增强的生长。该表型与炎症浸润减少有关，炎症浸润的减少特征在于包括NK细胞在内的几个白细胞群的募集受损。骨髓嵌合体显示非造血细胞区隔的CCRL2表达是导致在Kras突变型Ccrl2缺陷小鼠中观察到的肿瘤形成增加的原因。在人和小鼠的肺中，CCRL2由一小部分CD31 +内皮细胞表达，可以控制NK的浸润。人肺腺癌活检组织中CCRL2表达升高与临床结果呈正相关。这些结果提供了CCRL2在形成抗肺肿瘤免疫应答中的关键作用的证据。人肺腺癌活检组织中CCRL2表达升高与临床结果呈正相关。这些结果提供了CCRL2在形成抗肺肿瘤免疫应答中的关键作用的证据。人肺腺癌活检组织中CCRL2表达升高与临床结果呈正相关。这些结果提供了CCRL2在形成抗肺肿瘤免疫应答中的关键作用的证据。