Recombinant Mouse IL-28A/IFN-lambda 2 Protein

IL-28A (also named interferon-lambda 2, IFN-lambda 2), IL-28B (IFN-lambda 3) and IL-29 (IFN-lambda 1) are type III interferons that are class II cytokine receptor ligands (1 - 4). They are distantly related to members of the IL-10 family and type I IFN family (1 - 4). Mouse IL-28A cDNA encodes a 193 amino acid (aa) protein with a 19 aa signal peptide and a 174 aa mature protein that lacks N-glycosylation sites. Mature mouse IL-28A shares 81% and 66% aa sequence identity with rat and human IL-28A, respectively, and functions across species (5). Mouse IL-28A and IL-28B share 97% aa identity; the mouse lacks a functional IL-29 gene (4). Type III interferons are widely expressed, but are mainly produced by antigen presenting cells in response to viruses and double-stranded RNA that interact with Toll-like receptors or RIG-1 family helicases (2 - 6). They signal through a widely expressed receptor that is a heterodimer of the IL-10 receptor  beta (IL-10 R beta) and IL-28 receptor  alpha (IL-28 R alpha; also called IFN-lambda  R1) (2, 3, 7, 9). Interaction of either type I or type III IFNs with their receptors activates similar pathways, including JAK tyrosine kinase activation, STAT phosphorylation and formation of the IFN-stimulated regulatory factor 3 (ISGF-3) transcription factor complex (1 - 3). Both type I and III IFNs induce antiviral activity and upregulate MHC class I antigen expression (2 - 6). Cell lines responsive to type III IFNs are also responsive to type I IFNs, but in general, higher concentrations of type III IFNs are needed for similar in vitro responses (8). In vivo, however, type III IFNs enhance levels of IFN-gamma in serum, suggesting that the robust antiviral activity of type III IFNs may stem in part from activation of the immune system (5, 7). Anti-proliferative and antitumor activity in vivo has also been shown for type III IFNs (9 - 11).