Slfn2 Regulates Type I Interferon Responses by Modulating the NF-κB Pathway

Although members of the Slfn family have been implicated in the regulation of type I interferon (IFN) responses, the mechanisms by which they mediate their effects remain unknown. In the present study, we provide evidence that targeted disruption of the Slfn2 gene leads to increased transcription of IFN-stimulated genes (ISGs) and enhanced type I IFN-mediated antiviral responses. We demonstrate that Slfn2 interacts with protein phosphatase 6 regulatory subunit 1 (PPP6R1), leading to reduced type I IFN-induced activation of nuclear factor kappa B (NF-κB) signaling, resulting in reduced expression of ISGs. Altogether, these data suggest a novel mechanism by which Slfn2 controls ISG expression and provide evidence for a critical role for Slfn2 in the regulation of IFN-mediated biological responses.