Description:
<jats:title>Abstract</jats:title>
<jats:p>Type III interferon (IFN-λ) belongs functionally to the interferon family, although it is structurally related to IL-10 family of cytokines. We have used a reporter mouse lacking type I IFN receptor to identify IFN-λ-responsive cells in vivo by staining tissue sections with antibodies that recognize the IFN-induced Mx1 protein. We found that epithelial cells lining the respiratory, gastrointestinal and reproductive tracts are responding most strongly to IFN-λ stimulation. Additionally, IFN-λ-induced Mx1 was detectable in epithelial cells of the skin, placenta, fetal membranes, ovaries, mammory glands, cornea and conjunctiva. In vitro experiments on various epithelial cell lines not only confirmed this finding, but also demonstrated the potent antiviral activity of exogenous IFN-λ against a diverse set of viruses. Using knockout mice lacking either functional type I or type III IFN receptors, we demonstrated that IFN-λ is redundant to type I IFN functions in the lung upon infection with various respiratory viruses, whereas a predominant protection against rotavirus infection of the small intestinal epithelium was mediated by IFN-λ. Interestingly, mice lacking functional receptors for IFN-λ showed higher susceptibility not only to rotavirus, but also to another enteric virus, the reovirus. Taken together, a picture emerges showing that IFN-λ is a potent antiviral cytokine mediating protection against viral pathogens which infect the epithelium.</jats:p>