What Have We Learned from the IL28 Receptor Knockout Mouse?

Mordstein, Markus Michiels, Thomas [UCL] Staeheli, Peter

The recently discovered type III interferons (IFNs), also known as IFN-lambda, are part of the early innate immune response against viral infections. The IFN-lambda system closely resembles the type I IFN (IFN-alpha/beta) system in terms of expression after virus infection as well as intracellular signaling and activation of antiviral host factors in susceptible cells. However, in contrast to type I IFN, which signals through a universally expressed cell surface receptor, IFN-lambda uses a distinct receptor complex (IL28R) for signaling, which is expressed on a limited range of cell types. Until recently both the contribution of type III IFN to antiviral resistance as well as the exact nature of IL28R-expressing cells in vivo remained elusive. In this review we discuss data obtained from the experiments with IL28R alpha(0/0) mice that demonstrated the role of IFN-lambda in viral defense in vivo. We further discuss the experiments that identified the cell types in various organs that express functional IFN-lambda receptors.