Description: IFN-λs are a novel family of interferons which mediate the induction of anti-viral protection in a wide variety of cells. The three members of the IFN-λ family are λ1, λ2, and λ3, also known as IL-29, IL-28A, and IL-28B, respectively. IFN-λs share with type I IFNs an intracellular signaling pathway that drives the expression of a common set of IFN-stimulated genes. IFN-lambdas induce multiple biological activities, including the upregulation of class I MHC gene product expression to levels comparable to those induced by IFN-αs. IL-28 and IL-29 are tested for anti-viral activity by challenging the human hepatocellular carcinoma cell line HepG2 with infection by EMC (following pretreatment of the cells with cytokine).
Consistent with a role in anti-viral protection, the mRNA expression of IFN-lambdas is detectable in cells infected with various viruses. Moreover, monocyte-derived dendritic cells (important producers of IFN-α) express IFN-λ1 mRNA in response to treatment with dsRNA. TLR3 and TLR4 ligands induce IFN-α, IFN-β, IL-28, and IL-29 gene expression in macrophages; this is dependent upon IFN-α.
IFN-lambdas mediate their anti-viral protection through a class II cytokine receptor complex distinct from that of type I IFNs. This is comprised of two essential receptor proteins, CRF2-12/IFN-λR1, which is unique to IFN-lambdas, and CFR2-4/IL-10R2, which is shared with IL-10, IL-22, and IL-26 receptors. Whereas, the two chains of the type I IFN receptor (IFN-AR1 and IFN-AR2) and IL-10R2 are ubiquitously expressed, IFN-λR1 expression is limited and cell-type dependent. IFN-λR1 is not expressed by monocytes, but is up-regulated during GM-CSF/IL-4 induced differentiation of DCs from human monocytes, yielding iDCs which are fully responsive to IFN-λ.
The IFN-λs, IL-28 and IL-29, have recently been reported to prime dendritic cells to induce proliferation of Foxp3-bearing regulatory T cells. IFN-λ-matured DCs express high levels of class I and II MHC gene products, but low levels of costimulatory molecules, and are able to specifically induce IL-2-dependent proliferation of CD4+CD25+FOXP3+ T cell population with contact dependent suppressive activity on T cells.
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