Interferon regulatory factor 5 in Rheumatoid arthritis and systemic lupus erythematosus

Abstract

The interferon regulatory factor (IRF) family consists of nine members: IRF1, IRF2, IRF3, IRF4, IRF5, IRF6, IRF7, IRF8, and IRF9 [1]. In the 1980s, these proteins were described as transcriptional regulators of type I interferons (IFNs), including Ifnb and Ifna genes. The function of IRF and the production of IFNβ and IFNα form the first line of defense against viral infection. Type I IFN promotes degradation of viral DNA/RNA, inhibits viral replication and particle assembly, and enhances apoptosis in infected cells. It also enhances the differentiation of dendritic cells (DCs) and polarization of TH1 to enhance the antiviral immune response [2, 3]. The importance of these proteins is highlighted by the existence of viral-encoded IRF homologous of the host IRF, but with no function to circumvent the immune response [4-7]. The IRF protein binds to DNA by conserved N-terminal DNA binding domain, which is known as the interferon-stimulated response element (ISRE) [8]. The IRF also binds other transcription factors to enhance gene expression during the immune response. The Ifnb enhancer includes regulatory elements designated as positive regulatory domains (PRD). The transcription proteins consist of four positive regulatory domains: 1 NFkB dimer (RelA/p50), 1 AP1 complex (ATF2/c-Jun), and 2 heterodimers or homodimers of IRF, and assemble at the Ifnb promoter and promotes gene expression [9-14]. Some immune cells such as plasmacytoid dendritic cells are specialized to produce a large amount of IFNα. In this study, both IRF5 and IRF7 were expressed constitutively and played important roles in IFNα production [15]. In addition to antiviral immune response, IRF proteins could also play crucial roles in transcription regulations and the regulation of other immune responses. More importantly, IRF5 could be produced in different cell types such as macrophages, B cells, and DCs and has been associated with susceptibility to different autoimmune diseases [16]. Review Article Open Access