Upregulation of miR‐210‐5p in Systemic Lupus Erythematosus Impairs Silent Clearance of Dead Cell Remnants

Abstract

Deficiency of dead cell clearance plays a significant contributing factor in the progression of Systemic Lupus Erythematosus (SLE). While several studies support macrophage‐mediated innate immune response for SLE development, the mechanism about “silent” clearance by polarized monocyte/macrophage populations in SLE still needs to be elucidated. By analyzing miRNA level, the expression of miR‐210‐5p from peripheral blood mononuclear cells (PBMCs) in patients with active SLE (n=17) was higher than that in healthy controls (n=16). We further used macrophage‐like THP‐1 as cell models to delineate the status of miR‐210‐5p upregulation on silent clearance and immune response. By miR‐210‐5p mimic transfection, differentiation and phagocytosis analysis, miR‐210‐5p‐overexpression increased accumulation of secondary necrotic cells (SNECs) in THP‐1 cells. ROS production of miR‐210‐5p‐overexpressed macrophage‐like THP‐1 cells was decreased as compared with that in negative controls upon secondary necrotic cells (SNECs) or H2O2 treatment by DCF‐DA staining. Impaired SNECs clearance in miR‐210‐5p‐overexpressed THP‐1 cells was mediated by a decrease in superoxide production through NOX pathway. These findings support the notion that increased miR‐210‐5p in SLE is, in part, due to decrease the NOX‐mediated redox signaling, which affects impaired dead cell clearance and immune response.