Human IL-28A was initially identified in conjunction with IL-28B and IL-29 from human genomic sequences. They are distantly related to type I interferons (IFNs) and the IL-10 family. Like the IL-10 gene family, IL-28A, IL-28B, and IL-29 contain multiples exons. IL-28A and IL-28B share 96% amino acid identity, while IL-29 has 81% homology to IL-28A and IL-28B. Similar to type I IFNs, these three cytokines are induced by viral infections and possess antiviral activity. Thus, this family of cytokines is called lambda-interferons or type III interferons. IL-28/29 represents an evolutionary link between type I IFNs and the IL-10 family. The IL-28/29 cytokines bind to a heterodimeric receptor formed by IL-28Rα and IL-10Rβ, which is also part of the receptors for IL-10, IL-22, and IL-26. IL-10Rβ is widely expressed and IL-28Rα is restricted to epithelium like tissues (hepatocytes) and myeloid lineage cells such as dendritic cells and macrophages. IL-28A inhibits hepatitis C virus (HCV) replication, assembly, and release, without affecting HCV entry. Together, IL-28A and IFN-α suppress HCV replication. Type III Interferons, IL-28, and IL-29, are increased in chronic HCV Infection, and these interferons support the generation of dendritic cells (DC) populations with regulatory capacity, which facilitates expansion of Tregs.