Interleukin-28 (IL-28) is a cytokine that comes in two isoforms, IL-28A and IL-28B, and plays a role in immune defense against viruses, including the induction an "antiviral state" by turning on Mx proteins, 2',5'-oligoadenylate synthetase as well as ISGF3G (Interferon Stimulated Gene Factor 3).[1] IL-28A and IL-28B belong to the type III interferon family of cytokines and are highly similar (in amino acid sequence) to IL-29. Their classification as Interferons is due to their ability to induce an antiviral state, while their additional classification as cytokines is due to their chromosomal location as well as the fact that they are encoded by multiple exons, as apposed to a single exon, as most type-I IFNs are.
Discovery
IL-28 was discovered in 2003 by Zymogenetics[2] using a genomic screening process in which the entire human genone was scanned for putative genes. Once these genes were found, a second scan was performed to look specifically for cytokines. Both IL-28 and IL-29 were found in humans using this type of analysis.
Structure
IL-28 genes are located near IL-29 on chromosome 19 in humans. The two isoforms of IL-28 (IL-28A and IL-28B) are 96% homologous, although differences in the functions between the two forms remains unclear.
The receptor for IL-28 is composed of a unique IL-28Receptor Alpha chain which pairs with the IL-10Receptor Beta chain, leading many to classify IL-28 as a IL-10-like family member.
Function
IL-28 has also been shown to play a role in the adaptive immune response, as it's inclusion as an immunoadjuvant during small animal vaccination lead to augmented antigen-specific Interferon Gamma release as well as an increased cytotoxic potential in CD8+ T cells.
Clinical significance
Addition of IL-28 to vaccination results in 100% protection from a lethal H1N1 Influenza challenge in a small animal model when it was paired with an Influenza vaccine that protected only 50% of the time without IL-28.[3]
A single nucleotide polymorphism (SNP) near the IL28B gene predicts response to hepatitis C treatment with interferon and ribavirin.[4][5]
References
- ^ Kempuraj D, Donelan J, Frydas S, Iezzi T, Conti F, Boucher W, Papadopoulou NG, Madhappan B, Letourneau L, Cao J, Sabatino G, Meneghini F, Stellin L, Verna N, Riccioni G, Theoharides TC (2004). "Interleukin-28 and 29 (IL-28 and IL-29): new cytokines with anti-viral activities". Int J Immunopathol Pharmacol 17 (2): 103–6. PMID 15171810.
- ^ Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM (January 2003). "IL-28, IL-29 and their class II cytokine receptor IL-28R". Nat. Immunol. 4 (1): 63–8. doi:10.1038/ni873. PMID 12469119.
- ^ Morrow MP, Pankhong P, Laddy DJ, Schoenly KA, Yan J, Cisper N, Weiner DB (June 2009). "Comparative ability of IL-12 and IL-28B to regulate Treg populations and enhance adaptive cellular immunity". Blood 113 (23): 5868–77. doi:10.1182/blood-2008-11-190520. PMID 19304955.
- ^ PGxNews.Org (August 2009). "New biomarker predicts response to hepatitis C treatment". PGxNews.Org. http://www.pgxnews.org/web/pgx-pharmacogenomics-articles-reviews/40-pgx-pharmacogenomics-article-review/104-new-biomarker-predicts-response-to-hepatitis-c-treatment. Retrieved 2009-08-17.
- ^ Ge D, Fellay j, Thompson A, et al. (2009). "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance". Nature.
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Cell signaling: cytokines |
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IL-12 family
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Main
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TNF (ligand) superfamily
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