IFN-λ strongly acts on epithelial cells but with the exception of neutrophils, immune cells express no or only few functional receptors for IFN-λ. Accordingly, IFN-λ has been recognized as an important component of the innate immune system that protects the mucosa from viral attacks, but whether IFN-λ can also modulate adaptive immune responses has remained unknown. We found that mice lacking functional receptors for IFN-λ produced only low levels of serum IgG1 after intranasal immunization with a live-attenuated influenza virus. Bone marrow transfer experiments revealed that IFN-λ mediates its immune-enhancing effect by acting on non-hematopoietic cells. We further found that IFN-λ stimulates IgG1 production and confers enhanced antiviral protection when a viral antigen is administered to mice via the intranasal but not via the intraperitoneal or subcutaneous routes, indicating that epithelial cells secrete some immuno-regulatory factors when exposed to IFN-λ. By using knockout mice and neutralizing antibodies we demonstrate that thymic stromal lymphopoietin (TSLP) mediates the immune-enhancing effect of IFN-λ during mucosal immunization. Our results reveal a previously unknown collaboration between two unrelated cytokines that improves the crosstalk between antigen-exposed epithelial cells and immune cells. The newly discovered adjuvant activity of IFN-λ could improve the efficacy of mucosal vaccines against pathogens affecting humans and livestock.