IFIT5 Negatively Regulates the Type I IFN Pathway by Disrupting TBK1–IKKε–IRF3 Signalosome and Degrading IRF3 and IKKε

Abstract IFN-induced protein with tetratricopeptide repeats (IFITs), known as canonical IFN-stimulated genes (ISGs), play critical roles in regulating immune responses against pathogens and maintaining homeostasis. How the IFIT5 regulates innate is rarely reported remains enigmatic. In this study, we discover that human (hIFIT5) functions a negative regulator of type I IFN (IFN) pathway HEK293T cell lines. Our data illustrated hIFIT5 inhibited promotor activities IFN-β induced by IRF3 its upstream factors but not IRF3-5D (activated form IRF3), suggesting might be target hIFIT5. Further investigations revealed downregulated phosphorylation IKKε blocked nuclear translocation. Moreover, impaired IRF3–TBK1–IKKε complex, accompanied degradation. conclusion, these findings indicate modulator signaling pathway, opening additional avenues for preventing hyperactivation immunity