IL-29 is encoded by theIFNL1gene located onchromosome 19 in humans.[5][7] It is apseudogene 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 theIL-10 family, but its primaryamino acid sequence (and also function) is more similar to type I interferons.[5] It binds to aheterodimericreceptor composed of onesubunitIFNL1R specific for IFN-λ and a second subunitIL10RB shared among the IL-10 family cytokines.[5]
IL-29 expression is dominant in virus-infected epithelial cells of therespiratory,gastrointestinal andurogenital tracts, also in othermucosal tissues andskin. Hepatocytes infected byHCV orHBV 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 againstpathogens apart from viruses.[5] It affects the function of bothinnate andadaptive immune system. Besides described antiviral effects, IL-29 modulates cytokine production of other cells, for example, it increases secretion ofIL-6,IL-8 andIL-10 bymonocytes andmacrophages, enhances the responsiveness of macrophages toIFN-γ by increased expression ofIFNGR1, stimulatesT cell polarization towardsTh1 phenotype and alsoB cell response to IL-29 was reported.[8]
The impact of IL-29 oncancer cells is complicated depending on cancer cell type. It shows protective tumor inhibiting effects in many cases such asskin,lung,colorectal orhepatocellular cancer, but shows tumor promoting effects onmultiple myeloma cells.[6] IFN-λ have potential ascancer 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.
