Identification of a Predominantly Interferon-λ-Induced Transcriptional Profile in Murine Intestinal Epithelial Cells

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.