Regulatory dynamics ofin systemic lupus erythematosus: the interplay of type I interferon and c-Jun.

Abstract

OBJECTIVE: SLE is a multifaceted chronic inflammatory disorder characterised by a dysregulated immune response that involves various organ systems, with significant implications stemming from the type I interferon (IFN) signalling pathway in its pathogenesis. This study aimed to elucidate the contributory role of the IFN-induced protein 44-like () gene in SLE progression and to investigate its transcriptional regulatory mechanisms. METHODS: We quantifiedexpression in peripheral blood mononuclear cells of patients with SLE through quantitative PCR (qPCR), and established an in vitro THP-1 cell model overexpressingto assess its impact under IFN-α exposure using Cell Counting Kit-8 assays and flow cytometry. Additionally, we generatedknockout mice and Pristane-induced lupus mice to evaluate the influence ofon immune phenotypes and organ functionality. RESULTS: Our findings demonstrated thatis significantly expressed in CD3and CD14lymphocytes in patients with SLE, and under heightened IFN conditions, it plays a role in promoting cell proliferation while inhibiting apoptosis. Importantly,knockout mice exhibited ameliorated clinicopathological features of lupus, showing reduced haematological and renal damage. Furthermore, we identified c-Jun as a transcriptional factor that directly targets thepromoter, specifically activated by IFN-α in CD14lymphocytes. CONCLUSIONS: Our research indicates that IFN-α enhancesexpression via c-Jun, underscoring its critical role in the pathogenesis of SLE and suggesting potential pathways for therapeutic intervention.