POS0218 DECREASED miR-122-5p IN NEUTROPHIL-DERIVED EXOSOMES ATTENUATED IMMUNOREGULATORY FUNCTION ON MACROPHAGES BY TARGETING IRF5 EXPRESSION IN BEHCET’S DISEASE

Background Behçet’s disease (BD) is a chronic systemic vasculitis characterized by the overactivation of neutrophils and macrophages. Exosomes are membrane-derived vesicles that mediate intercellular communications neutrophil-derived exosomes account for major portion serum in BD. However, role BD remains unknown. Objectives 1) To investigate production neutrophils; 2) elucidate regulation macrophage exosomes; 3) explore mechanism immunoregulatory functions exosomes. Methods healthy control (HC) were extracted quantified. Human monocyte-derived macrophages (HMDM) stimulated with HC exosomes, TNF-α IL-6 examined. Differently expressed miRNAs analyzed using miRNA sequencing. LPS-induced HMDM treated mimics or inhibitors, detected. was overexpressed macrophages, RNA sequencing performed to analyze regulating pathways. Dual-luciferase assays confirm miRNA-mRNA interaction. Results produced significantly lower level than ones. Both suppressed but lesser extent Six downregulated presented including miR-122-5p. miR-122-5p inhibited while inhibitor promoted HMDMs. Overexpression attenuated TLR4 IFN-β signaling. directly targeted 3’UTR IRF5, TF pathway autocrine IFN-β, IRF5 expression confirmed dual luciferase assay. Knocking down dampened Figure 1. (A) Decreased (B) Reduced suppression activation (C) Differentially (downregulated) (D) JAK-STAT signaling HMDM. (E) (F) Conclusion Our findings suggested reduced function mediated levels Impaired might be implicated References [1]Kolonics, Ferenc et al. Cells vol. 9,12 2718. 18 Dec. 2020, Disclosure Interests None declared