IL-29 is encoded by the IFNL1gene located on chromosome 19 in humans.[5][7] It is a pseudogene in mice meaning the IL-29 protein is not produced in them.[5]
IL-29 is, with the rest of IFN-λ, structurally related to the IL-10 family, but its primary amino acid sequence (and also function) is more similar to type I interferons.[5] It binds to a heterodimericreceptor composed of one subunitIFNL1R specific for IFN-λ and a second subunit IL10RB shared among the IL-10 family cytokines.[5]
IL-29 expression is dominant in virus-infected epithelial cells of the respiratory, gastrointestinal and urogenital tracts, also in other mucosal tissues and skin. Hepatocytes infected by HCVorHBV viruses stimulate the immune response by producing IL-29 (IFN-λ in general) rather than type I interferons.[5][6] It is also produced by maturing macrophages, dendritic cells or mastocytes.[6]
It plays a role in defense against pathogens apart from viruses.[5] It affects the function of both innate and adaptive immune system. Besides described antiviral effects, IL-29 modulates cytokine production of other cells, for example, it increases secretion of IL-6, IL-8 and IL-10bymonocytes and macrophages, enhances the responsiveness of macrophages to IFN-γ by increased expression of IFNGR1, stimulates T cell polarization towards Th1 phenotype and also B cell response to IL-29 was reported.[8]
The impact of IL-29 on cancer cells is complicated depending on cancer cell type. It shows protective tumor inhibiting effects in many cases such as skin, lung, colorectalorhepatocellular cancer, but shows tumor promoting effects on multiple myeloma cells.[6] IFN-λ have potential as cancer therapy, with effects on more restricted cell types and fewer side-effects than type I interferons.[5][6]
Jordan WJ, Eskdale J, Boniotto M, Rodia M, Kellner D, Gallagher G (January 2007). "Modulation of the human cytokine response by interferon lambda-1 (IFN-lambda1/IL-29)". Genes and Immunity. 8 (1): 13–20. doi:10.1038/sj.gene.6364348. PMID17082759. S2CID40259925.
Wolk K, Witte K, Witte E, Proesch S, Schulze-Tanzil G, Nasilowska K, Thilo J, Asadullah K, Sterry W, Volk HD, Sabat R (May 2008). "Maturing dendritic cells are an important source of IL-29 and IL-20 that may cooperatively increase the innate immunity of keratinocytes". Journal of Leukocyte Biology. 83 (5): 1181–93. doi:10.1189/jlb.0807525. PMID18281438. S2CID46765523.
Witte K, Gruetz G, Volk HD, Looman AC, Asadullah K, Sterry W, Sabat R, Wolk K (December 2009). "Despite IFN-lambda receptor expression, blood immune cells, but not keratinocytes or melanocytes, have an impaired response to type III interferons: implications for therapeutic applications of these cytokines". Genes and Immunity. 10 (8): 702–14. doi:10.1038/gene.2009.72. PMID19798076. S2CID9721683.
Rauch A, Kutalik Z, Descombes P, Cai T, Di Iulio J, Mueller T, Bochud M, Battegay M, Bernasconi E, Borovicka J, Colombo S, Cerny A, Dufour JF, Furrer H, Günthard HF, Heim M, Hirschel B, Malinverni R, Moradpour D, Müllhaupt B, Witteck A, Beckmann JS, Berg T, Bergmann S, Negro F, Telenti A, Bochud PY (April 2010). "Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study". Gastroenterology. 138 (4): 1338–45, 1345.e1–7. doi:10.1053/j.gastro.2009.12.056. PMID20060832.
