LncRNA <i>PTPRE-AS1</i> modulates M2 macrophage activation and inflammatory diseases by epigenetic promotion of PTPRE.

Abstract

Long noncoding RNAs (lncRNAs) are important regulators of diverse biological processes; however, their function in macrophage activation is undefined. We describe a new regulatory mechanism, where an unreported lncRNA, <i>PTPRE-AS1</i>, targets receptor-type tyrosine protein phosphatase ε (PTPRE) to regulate macrophage activation. <i>PTPRE-AS1</i> was selectively expressed in IL-4-stimulated macrophages, and its knockdown promoted M2 macrophage activation via MAPK/ERK 1/2 pathway. In vivo, <i>PTPRE-AS1</i> deficiency enhanced IL-4-mediated M2 macrophage activation and accelerated pulmonary allergic inflammation while reducing chemical-induced colitis. Mechanistically, <i>PTPRE-AS1</i> bound WDR5 directly, modulating H3K4me3 of the <i>PTPRE</i> promoter to regulate <i>PTPRE</i>-dependent signaling during M2 macrophage activation. Further, the expression of <i>PTPRE-AS1</i> and <i>PTPRE</i> was significantly lower in peripheral blood mononuclear cells from patients with allergic asthma. These results provide evidence supporting the importance of <i>PTPRE-AS1</i> in controlling macrophage function and the potential utility of <i>PTPRE-AS1</i> as a target for controlling inflammatory diseases.