Interferon-Lambda: A New Addition to an Old Family

Abstract

The discovery and initial description of the interferon-λ (IFN-λ) family in early 2003 opened an exciting new chapter in the field of IFN research. There are 3 IFN-λ genes that encode 3 distinct but highly related proteins denoted IFN-λ1, -λ2, and -λ3. These proteins are also known as interleukin-29 (IL-29), IL-28A, and IL-28B, respectively. Collectively, these 3 cytokines comprise the type III subset of IFNs. They are distinct from both type I and type II IFNs for a number of reasons, including the fact that they signal through a heterodimeric receptor complex that is different from the receptors used by type I or type II IFNs. Although type I IFNs (IFN-α/β) and type III IFNs (IFN-λ) signal via distinct receptor complexes, they activate the same intracellular signaling pathway and many of the same biological activities, including antiviral activity, in a wide variety of target cells. Consistent with their antiviral activity, expression of the IFN-λ genes and their corresponding proteins is inducible by infection with many types of viruses. Therefore, expression of the type III IFNs (IFN-λs) and their primary biological activity are very similar to the type I IFNs. However, unlike IFN-α receptors which are broadly expressed on most cell types, including leukocytes, IFN-λ receptors are largely restricted to cells of epithelial origin. The potential clinical importance of IFN-λ as a novel antiviral therapeutic agent is already apparent. In addition, preclinical studies by several groups indicate that IFN-λ may also be useful as a potential therapeutic agent for other clinical indications, including certain types of cancer.