The Role of ChemR23 in the Induction and Resolution of Cigarette Smoke-Induced Inflammation
The Role of ChemR23 in the Induction and Resolution of Cigarette Smoke-Induced Inflammation
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DOI：
10.4049/jimmunol.1003862
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发表时间：
2011-05-01
影响因子：
4.4
通讯作者：
Joos, Guy F.
中科院分区：
文献类型：
--
作者：
Demoor, Tine;Bracke, Ken R.;Joos, Guy F.
慢性阻塞性肺疾病主要由吸烟（CS）引发，即使在戒烟后也会进展。CS诱导炎性细胞过度流入支气管肺泡腔和肺实质，这可能是由于化学引诱物及其各自受体之间的复杂相互作用。在慢性阻塞性肺疾病的小鼠CS模型中，我们研究了趋化因子样受体ChemR 23对CS暴露肺中炎症的诱导和消退的重要性。亚急性和慢性CS暴露增加了野生型（WT）小鼠支气管肺泡灌洗液（BAL）中ChemR 23配体和趋化因子chemerin的蛋白水平。此外，CS暴露WT小鼠气道中促炎趋化因子CXCL 1、CCL 2和CCL 20增加，伴随炎性中性粒细胞和单核细胞、CD 11b（hi）CD 103（-）和CD 11b（lo）CD 103（+）树突状细胞（DC）以及CD 4（+）和CD 8（+）T细胞的大量积聚。暴露于CS后，WT小鼠的肺实质中浸润有炎性中性粒细胞、CD 11b（hi）CD 103（-）DC和活化的CD 4（+）T细胞。CS诱导的炎症在ChemR 23基因敲除小鼠的BAL液和肺中严重减弱，涉及炎性趋化因子的诱导和炎性细胞的募集。中性粒细胞和CD 8（+）T细胞在WT小鼠的气道中持续存在，气道来源的常规DC在纵隔淋巴结中也是如此，至少在戒烟后14天。在CS暴露的ChemR 23基因敲除小鼠的BAL液中，在最终暴露后14天，T细胞有显著的延迟积累。我们的数据支持ChemR 23在引导先天性和适应性免疫细胞到CS暴露的肺中的作用。免疫学杂志，2011，186：5457-5467。
Chronic obstructive pulmonary disease is mainly triggered by cigarette smoke (CS) and progresses even after smoking cessation. CS induces an exaggerated influx of inflammatory cells to the bronchoalveolar space and lung parenchyma, likely resulting from a complex interplay between chemoattractants and their respective receptors. In a murine CS model of chronic obstructive pulmonary disease, we studied the importance of chemokine-like receptor ChemR23 for the induction and resolution of inflammation in CS-exposed lungs. Subacute and chronic CS exposure increased protein levels of the ChemR23 ligand and chemoattractant, chemerin, in bronchoalveolar lavage (BAL) fluid of wild-type (WT) mice. Moreover, the proinflammatory chemokines CXCL1, CCL2, and CCL20 were increased in the airways of CS-exposed WT mice, accompanied by a massive accumulation of inflammatory neutrophils and monocytes, CD11b(hi)CD103(-) and CD11b(lo)CD103(+) dendritic cells (DCs), and CD4(+) and CD8(+) T cells. The lung parenchyma of WT mice was infiltrated with inflammatory neutrophils, CD11b(hi)CD103(-) DCs, and activated CD4(+) T cells after CS exposure. CS-induced inflammation was severely attenuated in BAL fluid and lungs of ChemR23 knockout mice with regard to the induction of inflammatory chemokines and the recruitment of inflammatory cells. Neutrophils and CD8(+) T cells persisted in the airways of WT mice, as did the airway-derived conventional DCs in the mediastinal lymph nodes, for at least 14 d after smoking cessation. In the BAL fluid of CS-exposed ChemR23 knockout mice, there was a remarkable delayed accumulation of T cells 14 d after the final exposure. Our data support a role for ChemR23 in directing innate and adaptive immune cells to CS-exposed lungs. The Journal of Immunology, 2011, 186: 5457-5467.