Therefore, considering the overactivation of IFN-I signaling pathway is found in more than 60% of SLE patients and critical to the development of SLE (9, 21, 22), we investigated the role of EZH2 on the activation of IFN-I signaling pathway and EZH2 inhibitor’s therapeutic effects in an SLE mouse model which depends on IFN-I. Here, EZH2 is linked to systemic lupus erythematosus.