Characterization of IFNλ1 (IL-29) gene regulation and analysis of inter-individual variation of IFNλ1 levels (38.18)

• Published in: The Journal of immunology (1950) 2009-04, Vol.182 (1_Supplement), p.38-38.18
• Main Authors: Siegel, Rachael, Eskdale, Joyce, Gallagher, Grant
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.182.Supp.38.18

Type III interferons are a relatively new class of anti-viral cytokines comprised of three members: IFNλ1, 2 and 3. Through an uncharacterized mechanism, levels of IFNλ1 are reduced in bronchial epithelial cells of rhinovirus-infected asthmatics. In this study, we have examined the regulation of IFNλ1 transcription by utilizing BEAS-2B bronchial epithelial cells as a model system. We have identified the IFNλ1 minimal promoter region that is responsive to viral infection. Using fluorescent DNA footprinting of epithelial cells and purified peripheral blood mononuclear cells (PBMCs) stimulated with various mitogens, we are mapping the occupancy of transcription factor binding sites up to 4kb from the IFNλ1 transcription start site. Furthermore, we have identified key regulators such as NFκ-B that are involved in control of IFNλ1 expression in epithelial cells. Data obtained from a sample set of PBMCs stimulated with HSV has shown inter-individual variation in IFNλ1, both at the level of mRNA and protein production. These findings have been correlated with analysis of selected SNP haplotypes within the IFN-λ1 promoter. Genotyping of the IFNλ1promoter has led to identification of three major haplotypes, which may relate to variation in IFNλ1 levels. The data presented in this study represent an initial characterization of IFNλ1 gene regulation that can now be applied to understanding pathogenic regulation of IFNλ1.