Dataset related to article "The Atypical Receptor CCRL2 Is Essential for Lung Cancer Immune Surveillance."
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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 <em>Ccrl2</em> promoted tumor progression in urethane-induced and in <em>Kras</em> <sup>G12D/+</sup>/<em>p53</em> <sup>LoxP</sup> lung tumor mouse models. Similarly, a <em>Kras</em>-mutant lung tumor displayed enhanced growth in <em>Ccrl2</em>-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 <em>Kras</em>-mutant <em>Ccrl2</em>-deficient mice. In human and mouse lungs, CCRL2 was expressed by a fraction of CD31<sup>+</sup> 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.
CCRL2是一种非信号转导型七跨膜结构域受体。CCRL2可结合趋化素(chemerin),该蛋白可促进包括巨噬细胞与自然杀伤(NK)细胞在内的白细胞发生趋化作用。此外,CCRL2可在超敏反应、炎症性关节炎、实验性自身免疫性脑脊髓炎(experimental autoimmune encephalitis)等多种病理状态下调控炎症应答。本研究探讨了CCRL2在肺癌相关炎症调控中的作用。在乌拉坦(urethane)诱导的肺肿瘤小鼠模型以及<em>Kras</em><sup>G12D/+</sup>/<em>p53</em><sup>LoxP</sup>肺肿瘤小鼠模型中,<em>Ccrl2</em>基因敲除可促进肿瘤进展。同样,在<em>Ccrl2</em>缺陷小鼠体内,<em>Kras</em>突变型肺肿瘤的生长能力显著增强。该表型与炎症浸润减少相关,其特征为包括NK细胞在内的多种白细胞群体的募集受损。骨髓嵌合体实验证实,非造血细胞组分表达的CCRL2是导致<em>Kras</em>突变型且<em>Ccrl2</em>缺陷小鼠肿瘤形成增加的原因。在人类与小鼠肺部,CCRL2由部分CD31<sup>+</sup>内皮细胞表达,这类细胞可调控NK细胞的浸润过程。人类肺腺癌活检样本中升高的CCRL2表达水平与临床结局呈正相关。上述研究结果证实,CCRL2在构建抗肺癌免疫应答过程中发挥关键作用。



