IL- 28A (Interferon-lambda 2; IFN-lambda 2), IL-28B/IFN-lambda 3, and IL-29/IFN-lambda 1 are type III interferons which are distantly related to IL-10 family and type I IFN family cytokines. Mature human IL-28A is an approximately 22-25 kDa protein that shares 66% amino acid (aa) sequence identity with mouse and rat IL-28A and shows cross-species activity. It shares 96% and 70% aa sequence identity with human IL-28B and IL-29, respectively. Type III interferons are upregulated in response to viral infection, and they act predominantly on epithelial cells through a receptor complex that contains IL-10 R beta and IL-28 R alpha /IFN-gamma R1. Type III IFNs function as anti-viral molecules and induce the upregulation of MHC class I antigen. IL-28A promotes the Th1 polarization of dendritic cells in the airway (e.g. production of IL-12 p70 and IFN-gamma ) and inhibits Th2 and Th17 mediated inflammation. In the liver, however, the IL-28A induced Th1 cytokine response contributes to inflammation in T cell mediated hepatitis. IL-28A additionally exhibits anti-tumor activity, in part by enhancing IL-12 dependent anti-tumor CTL responses in vivo. In contrast, it is up-regulated in invasive bladder cancer where it promotes tumor cell migration
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