Agomir miRNA-150-5p alleviates pristane-induced lupus by suppressing myeloid dendritic cells activation and inflammation via TREM-1 axis

Triggering receptors expressed on myeloid cell-1 (TREM-1) has been shown to participate in inflammatory autoimmune diseases. Nevertheless, the detailed underlying mechanisms and therapeutic benefits remain elusive, especially in myeloid dendritic cells (mDCs) and systemic lupus erythematosus (SLE). In this study, we screen TREM-1 as one of the hub genes closely correlated with the progression of SLE and identify soluble TREM-1 (sTREM-1) in serum as a valuable diagnostic biomarker for SLE. Moreover, activation of TREM-1 by its agonist promotes activation and chemotaxis of mDCs and increases production of inflammatory cytokines and chemokines, showing higher expression of IL-6, TNF-α and MCP-1. Disorders of epigenetic processes including non-coding RNA give rise to SLE, resulting in complicated syndromes. Herein, we show that lupus mice display a unique miRNA signature in spleen, among which miR-150 is the most significantly expressed miRNA that targeting TREM-1 compared with wild type group. Transfection of miRNA-150-5p mimics directly suppresses the expression of TREM-1 by binding to its 3' UTR. Our in vivo experiments first indicates that administration of miR-150-5p agomir effectively ameliorates lupus symptoms. Intriguingly, miR-150 inhibits the over activation of mDCs through TREM-1 signal pathway in lymphatic organs and renal tissues. Overall, TREM-1 represents a potentially novel therapeutic target and we identify miR-150-5p as one of the mechanisms to alleviate lupus disease, which is attributable for inhibiting mDCs activation through TREM-1 signaling pathway.