Allergens as Immunomodulatory Proteins: The Cat Dander Protein Fel d 1 Enhances TLR Activation by Lipid Ligands
Allergens as Immunomodulatory Proteins: The Cat Dander Protein Fel d 1 Enhances TLR Activation by Lipid Ligands
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DOI：
10.4049/jimmunol.1300284
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发表时间：
2013-08-15
影响因子：
4.4
通讯作者：
Bryant, Clare
中科院分区：
文献类型：
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作者：
Herre, Jurgen;Groenlund, Hans;Bryant, Clare
过敏反应可由结构多样的过敏原引发。大多数过敏原是蛋白质，然而广泛的研究还没有揭示它们是如何启动过敏反应的，以及为什么无数其他吸入的蛋白质不是。在这些过敏原中，猫分泌的球蛋白FEL-1是一种主要的过敏原，与严重的过敏反应有关。在这项研究中，我们证明了与粉尘变应原Der p 2类似，FEL d 1通过固有受体TLR4和TLR2显著增强了信号传递。然而，与Der p 2相反，Fel d 1不通过模仿TLR4辅助受体MD2起作用，并且在体外不能稳定地与TLR4/MD2复合体结合。然而，FEL d 1确实与TLR4激动剂内毒素结合，提示脂转移机制可能参与了FEL d 1增强TLR信号的作用。我们还发现，狗变应原Can f6属于Lipocalin变应原的一个独特类别，具有与Fel d 1非常相似的性质。我们认为Fel d 1和Can f 6属于一组过敏原免疫调节蛋白，在哮喘等疾病中增强天然免疫信号并促进呼吸道超敏反应。
Allergic responses can be triggered by structurally diverse allergens. Most allergens are proteins, yet extensive research has not revealed how they initiate the allergic response and why the myriad of other inhaled proteins do not. Among these allergens, the cat secretoglobulin protein Fel d 1 is a major allergen and is responsible for severe allergic responses. In this study, we show that similar to the mite dust allergen Der p 2, Fel d 1 substantially enhances signaling through the innate receptors TLR4 and TLR2. In contrast to Der p 2, however, Fel d 1 does not act by mimicking the TLR4 coreceptor MD2 and is not able to bind stably to the TLR4/MD2 complex in vitro. Fel d 1 does, however, bind to the TLR4 agonist LPS, suggesting that a lipid transfer mechanism may be involved in the Fel d 1 enhancement of TLR signaling. We also show that the dog allergen Can f 6, a member of a distinct class of lipocalin allergens, has very similar properties to Fel d 1. We propose that Fel d 1 and Can f 6 belong to a group of allergen immunomodulatory proteins that enhance innate immune signaling and promote airway hypersensitivity reactions in diseases such as asthma.