Dectin-2 mediates Th2 immunity through the generation of cysteinyl leukotrienes.
Dectin-2 mediates Th2 immunity through the generation of cysteinyl leukotrienes.
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DOI：
10.1084/jem.20100793
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发表时间：
2011-03-14
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;Rahman OM;Fernandez JM;Parsons MW;Xing W;Austen KF;Kanaoka Y
在体内，针对屋尘螨（Dermatophagoides farinae），GM - CSF培养的骨髓细胞上Dectin - 2的表达对于产生半胱氨酰白三烯和Th2细胞因子是必需的。
吸入性抗原激活Th2免疫的固有信号通路尚未明确界定。我们先前发现Dectin - 2是屋尘螨（Dermatophagoides farinae，Df）变应原提取物中聚糖的受体，它介导肺CD11c⁺细胞以及GM - CSF培养的骨髓细胞（BMCsGM - CSF）产生半胱氨酰白三烯（cys - LT）。通过在BMCsGM - CSF中使用慢病毒敲低Dectin - 2，并将Df脉冲的BMCsGM - CSF过继转移以使未致敏小鼠致敏，我们现在报道Dectin - 2对于Df诱发的嗜酸性和中性粒细胞性肺部炎症以及肺和再刺激淋巴结中Th2细胞因子的产生至关重要。用来自LTC4合酶（LTC4S）缺陷小鼠或1型半胱氨酰白三烯受体（CysLT1R）缺陷小鼠的Df脉冲的BMCsGM - CSF致敏表明，这两种蛋白对于Df诱发的嗜酸性肺部炎症以及肺和再刺激淋巴结中Th2细胞因子的产生都是必需的。对Ltc4s⁻/⁻和Cysltr1⁻/⁻小鼠直接致敏和激发证实半胱氨酰白三烯介导了Df诱发的Th2肺部炎症的这些参数。因此，Dectin - 2 - 半胱氨酰白三烯通路对于针对一种主要变应原诱导Th2免疫至关重要，部分是通过CysLT1R。这些发现确定了一种此前未被认识的髓样C型凝集素受体与Th2免疫之间的联系。
Dectin-2 expression on GM-CSF–cultured bone marrow cells is required for the generation of cysteinyl leukotrienes and Th2 cytokines in response to the house dust mite Dermatophagoides farinae in vivo. The innate signaling pathways for Th2 immunity activated by inhaled antigens are not well defined. We previously identified Dectin-2 as a receptor for glycans in allergen extracts from the house dust mite Dermatophagoides farinae (Df) that mediates cysteinyl leukotriene (cys-LT) generation from pulmonary CD11c+ cells and from GM-CSF–cultured bone marrow cells (BMCsGM-CSF). Using lentiviral knockdown of Dectin-2 in BMCsGM-CSF and adoptive transfer of Df-pulsed BMCsGM-CSF to sensitize naive mice, we now report that Dectin-2 is critical for the development of Df-elicited eosinophilic and neutrophilic pulmonary inflammation and Th2 cytokine generation in the lungs and restimulated lymph nodes. Sensitization with Df-pulsed BMCsGM-CSF from LTC4 synthase (LTC4S)–deficient mice or type 1 cys-LT receptor (CysLT1R)–deficient mice demonstrated that both proteins were required for Df-elicited eosinophilic pulmonary inflammation and Th2 cytokine generation in the lungs and restimulated lymph nodes. Direct sensitization and challenge of Ltc4s−/− and Cysltr1−/− mice confirmed that cys-LTs mediate these parameters of Df-elicited Th2 pulmonary inflammation. Thus, the Dectin-2–cys-LT pathway is critical for the induction of Th2 immunity to a major allergen, in part through CysLT1R. These findings identify a previously unrecognized link between a myeloid C-type lectin receptor and Th2 immunity.
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影响因子：
4.3
作者：
Meyer, Sandra;Tefsen, Boris;van Die, Irma
通讯作者：
van Die, Irma
影响因子：
6.1
作者：
Instanes, C;Ormstad, H;Hetland, G
通讯作者：
Hetland, G
影响因子：
4.8
作者：
Maekawa, A;Austen, KF;Kanaoka, Y
通讯作者：
Kanaoka, Y
影响因子：
15.9
作者：
Lambrecht, BN;De Veerman, M;Pauwels, RA
通讯作者：
Pauwels, RA
DOI：
10.1073/pnas.96.18.10338
发表时间：
1999-08-31
影响因子：
11.1
作者：
Madsen, L;Labrecque, N;Fugger, L
通讯作者：
Fugger, L