Recognition of double-stranded RNA by TLR3 induces severe small intestinal injury in mice
Recognition of double-stranded RNA by TLR3 induces severe small intestinal injury in mice
复制标题
TLR3识别双链RNA诱导小鼠严重小肠损伤
DOI：
10.4049/jimmunol.178.7.4548
复制
发表时间：
2007-04-01
影响因子：
4.4
通讯作者：
Tian, Zhigang
中科院分区：
文献类型：
--
作者：
Zhou, Rongbin;Wei, Haiming;Tian, Zhigang
TLRs对肠上皮细胞（IEC）的作用是有争议的，TLRs影响粘膜稳态的机制尚不清楚。在这项研究中，我们报告了轮状病毒的基因组dsRNA及其合成类似物聚肌苷酸-聚胞苷酸（poly（I：C））诱导小肠严重的粘膜损伤。在将TLR 3结合到IEC上后，dsRNA触发IEC分泌IL-15，其功能是增加CD 3（+）NK1.1（+）肠上皮内淋巴细胞（IEL）的百分比并增强IEL的细胞毒性。此外，CD 3（+）NK1.1（+）IEL被证明是CD 8 α α（+）IEL。这些结果提供了异常TLR 3信号传导有助于破坏粘膜稳态的直接证据，以及CD 8 α α（+）IEL介导的致病作用的第一个证据。这些数据还表明，基因组dsRNA可能参与急性轮状病毒胃肠炎的发病机制。
The role of TLRs on intestinal epithelial cells (IECs) is controversial, and the mechanisms by which TLRs influence mucosal homeostasis are obscure. In this study, we report that genomic dsRNA from rotavirus, and its synthetic analog polyinosinic-polycytidylic acid (poly(I:C)), induce severe mucosal injury in the small intestine. Upon engaging TLR3 on IECs, dsRNA triggers IECs to secrete IL-15, which functions to increase the percentage of CD3(+)NK1.1(+) intestinal intraepithelial lymphocytes (IELs) and enhances the cytotoxicity of IELs. Moreover, The CD3(+)NK1.1(+) IELs are proved as CD8 alpha alpha(+) IELs. These results provide direct evidence that abnormal TLR3 signaling contributes to breaking down mucosal homeostasis and the first evidence of pathogenic effects mediated by CD8 alpha alpha(+) IELs. The data also suggest that genomic dsRNA may be involved in the pathogenesis of acute rotavirus gastroenteritis.