Dectin-2 recognition of house dust mite triggers cysteinyl leukotriene generation by dendritic cells.
Dectin-2 recognition of house dust mite triggers cysteinyl leukotriene generation by dendritic cells.
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DOI：
10.4049/jimmunol.182.2.1119
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发表时间：
2009-01-15
期刊：
影响因子：
--
通讯作者：
Kanaoka Y
中科院分区：
文献类型：
--
作者：
Barrett NA;Maekawa A;Rahman OM;Austen KF;Kanaoka Y
屋尘螨是全球空气传播过敏原的重要来源，但人们对它们如何如此有效地引发过敏性炎症知之甚少。我们发现，粉尘螨(DF)和屋尘螨和霉菌烟曲霉菌的提取物能刺激小鼠骨髓来源的树突状细胞(BMDCs)快速而强劲地产生促炎症脂质介质--半胱氨酰白三烯(Cys-LTS)。ConA亲和层析显示，相关的配基是一个糖链(S)，提示是通过树突状细胞(DC)凝集素受体刺激的。来自野生型小鼠的BMDCs产生的Cys-LT可被脾酪氨酸激酶(Syk)抑制剂抑制，而在fcrγ−/−小鼠的BMDCs中则被取消，这可能与Dectin-2或DC免疫激活受体有关。将每种受体分别导入骨髓来源的肥大细胞，发现只有Dectin-2能介导DF、屋尘埃和烟曲霉菌产生Cys-LT。慢病毒敲除BMDCs中Dectin-2可减弱DF提取物诱导的Cys-LT生成，从而确定Dectin-2为受体。肺CD11c+细胞，而不是腹膜或肺泡巨噬细胞，也产生了对DF的反应的Cys-LT。这些发现将Dectin-2置于激活花生四烯酸代谢的C型凝集素受体中，并确认Dectin-2/FCRSyk/Cys-LT轴是三种有效的室内变应原激活天然免疫细胞促进变应性炎症的新机制。
House dust mites are a significant source of airborne allergen worldwide, but there is little understanding of how they so potently generate allergic inflammation. We found that extracts from the house dust mites Dermatophagoides farinae (Df) and Dermatophagoides pteronyssinus and from the mold Aspergillus fumigatus stimulated a rapid and robust production of cysteinyl leukotrienes (cys-LTs), proinflammatory lipid mediators, from mouse bone marrow-derived dendritic cells (BMDCs). Con A affinity chromatography of the Df extract revealed that the relevant ligand is a glycan(s), suggesting stimulation via a dendritic cell (DC) lectin receptor. Cys-LT production in BMDCs from wild-type mice was inhibited by spleen tyrosine kinase (Syk) inhibitors and was abolished in BMDCs from FcRγ−/− mice, implicating either Dectin-2 or DC immunoactivating receptor. Transfection of each receptor in bone marrow-derived mast cells revealed that only Dectin-2 mediates cys-LT production by Df, Dermatophagoides pteronyssinus, and Aspergillus fumigatus. Lentiviral knockdown of Dectin-2 in BMDCs attenuated Df extract-elicited cys-LT generation, thereby identifying Dectin-2 as the receptor. Lung CD11c+ cells, but not peritoneal or alveolar macrophages, also generated cys-LTs in response to Df. These findings place Dectin-2 among the C-type lectin receptors that activate arachidonic acid metabolism and identify the Dectin-2/FcRγ/Syk/cys-LT axis as a novel mechanism by which three potent indoor allergens may activate innate immune cells to promote allergic inflammation.
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作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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