Mechanisms of innate immune activation by gluten peptide p31-43 in mice
Mechanisms of innate immune activation by gluten peptide p31-43 in mice
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DOI：
10.1152/ajpgi.00435.2015
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发表时间：
2016-07-01
影响因子：
4.5
通讯作者：
Chirdo, Fernando G.
中科院分区：
文献类型：
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作者：
Araya, Romina E.;Gomez Castro, Maria Florencia;Chirdo, Fernando G.
乳糜泻（CD）是一种由麸质引发的免疫介导的肠病，遗传易感个体。先天免疫参与了CD的发病机制，但其机制仍不清楚。虽然先前的体外研究表明麦胶蛋白肽p31-43作为先天免疫触发剂，但其潜在的途径尚不清楚，也没有在体内进行过探索。在这里，我们表明，p31-43的腔内递送诱导正常小鼠小肠粘膜的形态学变化与CD中所见一致，包括增加细胞死亡和炎症介质的表达。p31-43的作用依赖于MyD 88和I型IFN，但不依赖于Toll样受体4（TLR 4），并且通过共施用TLR 3激动剂聚肌胞苷酸（polyinosinic：polycytidylic acid）而增强。总之，这些结果表明麦胶蛋白肽p31-43在体内激活与CD相关的先天免疫途径，例如IFN依赖性炎症。我们的研究结果还表明，在CD的发病机制中，饮食麸质和病毒感染之间存在潜在的相互作用。
Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. Innate immunity contributes to the pathogenesis of CD, but the mechanisms remain poorly understood. Although previous in vitro work suggests that gliadin peptide p31-43 acts as an innate immune trigger, the underlying pathways are unclear and have not been explored in vivo. Here we show that intraluminal delivery of p31-43 induces morphological changes in the small intestinal mucosa of normal mice consistent with those seen in CD, including increased cell death and expression of inflammatory mediators. The effects of p31-43 were dependent on MyD88 and type I IFNs, but not Toll-like receptor 4 (TLR4), and were enhanced by coadministration of the TLR3 agonist polyinosinic: polycytidylic acid. Together, these results indicate that gliadin peptide p31-43 activates the innate immune pathways in vivo, such as IFN-dependent inflammation, relevant to CD. Our findings also suggest a common mechanism for the potential interaction between dietary gluten and viral infections in the pathogenesis of CD.