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Publication : Recognition of double-stranded RNA by TLR3 induces severe small intestinal injury in mice.

First Author  Zhou R Year  2007
Journal  J Immunol Volume  178
Issue  7 Pages  4548-56
PubMed ID  17372013 Mgi Jnum  J:145138
Mgi Id  MGI:3833543 Doi  10.4049/jimmunol.178.7.4548
Citation  Zhou R, et al. (2007) Recognition of double-stranded RNA by TLR3 induces severe small intestinal injury in mice. J Immunol 178(7):4548-56
abstractText  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 CD8alphaalpha+ 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 CD8alphaalpha+ IELs. The data also suggest that genomic dsRNA may be involved in the pathogenesis of acute rotavirus gastroenteritis.
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