Abstract
Type I (α and β) and type III (λ) interferons (IFNs) induce the expression of a large set of antiviral effector molecules via their respective surface membrane receptors. Whereas most cell types respond to type I IFN, type III IFN preferentially acts on epithelial cells and protects mucosal organs such as the lung and gastrointestinal tract. Despite the engagement of different receptor molecules, the type I and type III IFN-induced signaling cascade and upregulated gene profile is thought to be largely identical. Here, we comparatively analyzed the response of gut epithelial cells to IFN-β and IFN-λ2 and identified a set of genes predominantly induced by IFN-λ2. We confirm the influence of epithelial cell polarization for enhanced type III receptor expression and demonstrate the induction of predominantly IFN-λ2-induced genes in the gut epithelium in vivo. Our results suggest that IFN-λ2 targets the epithelium and induces genes to adjust the antiviral host response to the requirements at mucosal body sites.
Highlights
The interferon (IFN) family of cytokines acts to confer protection against various pathogens
The intestinal epithelial cell line (IEC) Mx2Luc was generated from a transgenic mouse containing the firefly luciferase gene under control of the myxovirus (influenza virus) resistance 2 (Mx2) promoter region as described earlier [32]
The recently described intestinal epithelial IEC10 cells exhibit many properties of the natural epithelium. They respond to both type I and type III IFNs and generate a robust antiviral state making them an ideal model to study IFN-induced gene expression [32]
Summary
The interferon (IFN) family of cytokines acts to confer protection against various pathogens. They are categorized into three different types. Type I and type III IFNs are secreted by a wide range of different cell types upon innate immune stimulation. Type I and III IFNs share low amino acid similarity (15–20%) and bind to structurally very different heterodimeric receptor complexes comprised of the IFN-α receptor (IFNAR) 1 and 2 chain as well as the IFN-λ receptor (IFN-λR) 1 and the IL-10 receptor (IL-10R)β chain, respectively [2, 3]. The type I IFN receptor is ubiquitously expressed by all nucleated cells differences in the expression level and functional sensiti vity have been reported [8, 9]. The type III IFN receptor is restricted to epithelial cells
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