AKT2 reduces IFNβ1 production to modulate anti-viral responses and systemic lupus erythematosus

ABSTRACT: Interferon regulatory factor 3 (IRF3)-induced type I interferon (I-IFN) production plays key roles in both anti-viral and autoimmune responses. IRF3 phosphorylation, dimerization and nuclear localization are needed for its activation and function, but the precise regulatory mechanisms remain to be explored. Here, we show that the serine/threonine kinase AKT2 interacts with IRF3 and phosphorylates it on Thr207, thereby attenuating IRF3 nuclear translocation in a 14-3-3ε-dependent manner and reducing I-IFN production. We further find that AKT2 expression is downregulated in viral-infected macrophages or in monocytes and tissue samples from systemic lupus erythematosus (SLE) patients and mouse models. Akt2-deficient mice exhibit increased I-IFN induction and reduced mortality in response to

SUBMITTER: Dr. Hongyan Wang 

PROVIDER: S-SCDT-EMBOJ-2021-108016 | biostudies-other |

REPOSITORIES: biostudies-other