FRI0003\u2005THE FUNCTION OF IRF7 SNP ON THE PRODUCTION OF TYPE I INTERFERON

Abstract

Background Type I IFN plays a significant role in the pathogenesis of Systemic Lupus Erythmatosus (SLE). IRF7 is a critical transcriptional factor for the production of type I interferons (IFN). Objectives To explore potential mechanisms for the SLE related IRF7 SNP on type I IFN production, which might indicate new theoretical basis for genetic therapeutic strategy. Methods We constructed different genotypes of SLE relevant SNP cell lines by Crispr/Cas9 technology, and confirmed them by sequencing. After TLR-ligand stimulation,the mRNA expression of IFNα was detected by real-time qPCR. The levels of IFNα, TNFα and IL-6 were detected by ELISA kit. The protein expression of IRF7/p-IRF7 was detected by western blot.The binding ability of endogenous IRF7 with typeIIFN promoter was studied by chromatin immunoprecipitation. Results We got IRF7 SNP rs1131665 GG/AA cell lines by gene editing technique. After TLR-ligand stimulation, IRF7 SNP rs1131665 AA cell line showed higher IFNα expression than GG, which indicated statistical significance. IRF7 SNP rs1131665 AA cell line showed higher p-IRF7 expression than GG detected with western blot. Endogenous IRF7 in IRF7 SNP rs1131665 AA cell line showed stronger binding ability with IFNα promoter than GG, which indicated statistical significance. Conclusion The missense variant of G to A in IRF7 SNP rs1131665, increased the production of typeIIFN, which indicated that IRF7 G to A missense variant increased the susceptibility of type I IFN associated diseases. References [1] Lin LH, Ling P, Liu MF.The potential role of interferon-regulatory factor 7 among Taiwanese patients with systemic lupus erythematosus.J Rheumatol. 2011,38(9):1914-1919. [2] Xu WD, Zhang YJ, Xu K, et al. IRF7, a functional factor associates with systemic lupus erythematosus. Cytokine. 2012,58(3):317-320. [3] Miyagawa F, Tagaya Y, Ozato K, et al.Essential Requirement for IFN Regulatory Factor 7 in Autoantibody Production but Not Development of Nephritis in Murine Lupus.J Immunol. 2016,197(6):2167-2176. Disclosure of Interests None declared