University of Nice-Sophia Antipolis, U924, Valbonne, France.
Nat Med. 2010 Nov;16(11):1305-12. doi: 10.1038/nm.2253. Epub 2010 Oct 31.
Allergic asthma is a T helper type 2 (T(H)2)-dominated disease of the lung. In people with asthma, a fraction of CD4(+) T cells express the CX3CL1 receptor, CX3CR1, and CX3CL1 expression is increased in airway smooth muscle, lung endothelium and epithelium upon allergen challenge. Here we found that untreated CX3CR1-deficient mice or wild-type (WT) mice treated with CX3CR1-blocking reagents show reduced lung disease upon allergen sensitization and challenge. Transfer of WT CD4(+) T cells into CX3CR1-deficient mice restored the cardinal features of asthma, and CX3CR1-blocking reagents prevented airway inflammation in CX3CR1-deficient recipients injected with WT T(H)2 cells. We found that CX3CR1 signaling promoted T(H)2 survival in the inflamed lungs, and injection of B cell leukemia/lymphoma-2 protein (BCl-2)-transduced CX3CR1-deficient T(H)2 cells into CX3CR1-deficient mice restored asthma. CX3CR1-induced survival was also observed for T(H)1 cells upon airway inflammation but not under homeostatic conditions or upon peripheral inflammation. Therefore, CX3CR1 and CX3CL1 may represent attractive therapeutic targets in asthma.
过敏性哮喘是一种以 Th2 细胞（T(H)2）为主导的肺部疾病。在哮喘患者中，一部分 CD4+ T 细胞表达 CX3CR1 受体，在过敏原刺激后，气道平滑肌、肺内皮细胞和上皮细胞中 CX3CL1 的表达增加。在这里，我们发现未经治疗的 CX3CR1 缺陷小鼠或用 CX3CR1 阻断剂处理的野生型（WT）小鼠在过敏原致敏和激发后肺疾病减轻。将 WT CD4+ T 细胞转移到 CX3CR1 缺陷小鼠中，恢复了哮喘的主要特征，并且 CX3CR1 阻断剂可防止 WT T(H)2 细胞注射到 CX3CR1 缺陷受者的气道炎症。我们发现 CX3CR1 信号促进了炎症肺部中的 T(H)2 细胞存活，并且将 B 细胞白血病/淋巴瘤-2 蛋白（BCl-2）转导的 CX3CR1 缺陷 T(H)2 细胞注入 CX3CR1 缺陷小鼠中可恢复哮喘。在气道炎症但不在稳态或外周炎症下，也观察到 CX3CR1 诱导的 Th1 细胞存活。因此，CX3CR1 和 CX3CL1 可能是哮喘的有吸引力的治疗靶点。
