Interleukin 28B (interferon-λ 3) is a protein that in humans is encoded by the IL28B gene. IL28B has recently been renamed IFNL3 as its official gene symbol.
This gene encodes a cytokine distantly related to type I interferons and the IL-10 family. This gene, interleukin 28A (IL28A), and interleukin 29 (IL29) are three closely related cytokine genes that form a cytokine gene cluster on a chromosomal region mapped to 19q13. Expression of the cytokines encoded by the three genes can be induced by viral infection. All three cytokines have been shown to interact with a heterodimeric class II cytokine receptor that consists of interleukin 10 receptor, beta (IL10RB) and interleukin 28 receptor, alpha (IL28RA). [provided by RefSeq, Jul 2008].
In individuals with chronic hepatitis C, the presence of specific polymorphisms near the IL28B gene has been associated with an increased response in treatment for the condition with interferon and ribavirin. The same polymorphisms were also demonstrated at higher frequencies in individuals infected with hepatitis C who cleared the infection spontaneously, compared to those that developed chronic hepatitis from the condition. A functional variant that determines the production of an antiviral protein has been linked to the polymorphisms in IL28B and implicated in the clearance of hepatitis C virus.
A non-coding genetic polymorphism (rs4803217) has been shown to significantly change the RNA structure and translation of IFNL3. The dynamic structure of the non-coding RNA produced by the rs4803217 polymorphism may be responsible for the increased HCV clearance of this allele.
^Lu YF, Goldstein DB, Urban TJ, Bradrick SS (Feb 2015). "Interferon-λ4 is a cell-autonomous type III interferon associated with pre-treatment hepatitis C virus burden". Virology. 476: 334–40. doi:10.1016/j.virol.2014.12.020. PMID25577150.
^Lu YF, Mauger DM, Goldstein DB, Urban TJ, Weeks KM, Bradrick SS (Nov 2015). "IFNL3 mRNA structure is remodeled by a functional non-coding polymorphism associated with hepatitis C virus clearance". Scientific Reports. 5: 16037. doi:10.1038/srep16037. PMID26531896.
Mennechet FJ, Uzé G (Jun 2006). "Interferon-lambda-treated dendritic cells specifically induce proliferation of FOXP3-expressing suppressor T cells". Blood. 107 (11): 4417–4423. doi:10.1182/blood-2005-10-4129. PMID16478884.
Li MC, Wang HY, Wang HY, Li T, He SH (Apr 2006). "Liposome-mediated IL-28 and IL-29 expression in A549 cells and anti-viral effect of IL-28 and IL-29 on WISH cells". Acta Pharmacologica Sinica. 27 (4): 453–459. doi:10.1111/j.1745-7254.2006.00292.x. PMID16539846.
Lasfar A, Lewis-Antes A, Smirnov SV, Anantha S, Abushahba W, Tian B, Reuhl K, Dickensheets H, Sheikh F, Donnelly RP, Raveche E, Kotenko SV (Apr 2006). "Characterization of the mouse IFN-lambda ligand-receptor system: IFN-lambdas exhibit antitumor activity against B16 melanoma". Cancer Research. 66 (8): 4468–4477. doi:10.1158/0008-5472.CAN-05-3653. PMID16618774.
Dellgren C, Gad HH, Hamming OJ, Melchjorsen J, Hartmann R (Mar 2009). "Human interferon-lambda3 is a potent member of the type III interferon family". Genes and Immunity. 10 (2): 125–131. doi:10.1038/gene.2008.87. PMID18987645.
Li M, Liu X, Zhou Y, Su SB (Jul 2009). "Interferon-lambdas: the modulators of antivirus, antitumor, and immune responses". Journal of Leukocyte Biology. 86 (1): 23–32. doi:10.1189/jlb.1208761. PMID19304895.