Dectin-1 plays a critical role in HDM-induced PGE<sub>2</sub> production in macrophages
Dectin-1 plays a critical role in HDM-induced PGE<sub>2</sub> production in macrophages
复制标题
Dectin-1 在 HDM 诱导巨噬细胞中 PGE<sub>2</sub> 产生中发挥关键作用
DOI：
10.1016/j.alit.2017.05.001
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发表时间：
2017
影响因子：
6.8
通讯作者：
Nakajima H.
中科院分区：
文献类型：
--
作者：
Ito T;Hirose K;Norimoto A;Saku A;Nakajima H.
哮喘是一种慢性变态反应性炎症性疾病，其特征是大量嗜酸性粒细胞和淋巴细胞浸润，粘液过度生成，以及由多种刺激引起的呼吸道高反应性。这些病理特征主要由抗原特异性Th2细胞及其细胞因子IL-4、IL-5和IL-13介导。1在大多数患者中，疾病活动是通过吸入皮质类固醇和长效b2激动剂或不使用长效b2激动剂来控制的；然而，在严重哮喘患者中，这些症状对这些标准治疗难以奏效，往往导致急诊和住院。虽然重症哮喘的发病机制尚不清楚，但已有研究表明哮喘的严重程度与对真菌的敏感度呈正相关。2此外，有研究表明，痰中中性粒细胞的数量与哮喘的严重程度有关。3考虑到中性粒细胞增多是Th17细胞介导的炎症的特征，而中性粒细胞对真菌的有效保护是必不可少的，这些发现提示Th17细胞可能参与了重症哮喘的发病机制。Dectin-1是一种识别真菌细胞壁成分b-葡聚糖的C型凝集素受体，参与Th17细胞的发育。4最近，我们发现，在肺内的树突状细胞(DC)亚群中，CD11būDC上表达Dectin-1，5 CD11b是变态反应性气道炎症发生发展所必需的DC亚群。此外，我们还发现CD11bū树突状细胞上表达的Dectin-1参与了屋尘螨诱导哮喘模型肺内Th2细胞和Th17细胞的诱导。5此外，我们还发现Dectin-1信号通过诱导趋化因子受体的表达来促进DC从肺向引流淋巴结的迁移。5虽然这些发现强调了CD11bū树突状细胞上表达的Dectin-1在HDM诱导的过敏性气道炎症中的重要性，但对肺内其他类型细胞上表达的Dectin-1的作用知之甚少。
Asthma is a chronic allergic inflammatory disease characterized by intense eosinophil and lymphocyte infiltration, mucus hyperproduction, and airway hyperresponsiveness, which is caused by a variety of stimuli. These pathological features are mainly mediated by antigen-specific Th2 cells and their cytokines, including IL-4, IL-5, and IL-13. 1 In the majority of patients, disease activities are controlled by inhaled corticosteroids with or without long acting b2 agonist; however, in patients with severe asthma, the symptoms are refractory to these standard treatments, and often lead to emergency visits and hospitalization. Although the mechanisms underlying the development of severe asthma are poorly understood, it has been shown that severity of asthma is positively correlated with the sensitization to fungi. 2 Furthermore, it has been shown that the number of neutrophils in sputum is associated with the severity of asthma. 3 Considering that neutrophilia is a characteristic feature of Th17 cell-mediated inflammation, which is essential for the efficient protection against fungi, these findings suggest that Th17 cells may be involved in the pathogenesis of severe asthma.Dectin-1 is a C-type lectin receptor that recognizes fungal cell wall component b-glucan, and is involved in the development of Th17 cells. 4 Recently, we have shown that, among dendritic cell (DC) subsets in the lung, dectin-1 is expressed on CD11b ū DCs, 5 an essential DC subset for the development of allergic airway inflammation. Moreover, we have shown that dectin-1 expressed on CD11b ū DCs is involved in the induction of Th2 cells as well as Th17 cells in the lung in house dust mite (HDM)-induced asthma models. 5 Furthermore, we found that dectin-1 signaling enhances the migration of DCs from the lung to draining lymph nodes by inducing the expression of chemokine receptors. 5 Although these findings highlight the importance of dectin-1 expressed on CD11b ū DCs in HDM-induced allergic airway inflammation, little is known about the roles of dectin-1 expressed on other cell types in the lung.