ExRNA Takes a Toll in Sepsis-associated Lung Injury

Lam and Mangalmurti discuss the role of ExRNA in sepsis-associated lung injury. Extracellular RNA (exRNA) is primarily composed of microRNA (miRNA) and ribosomal RNA (rRNA) and can be vesicle-associated, protein-bound, or free form. These different forms of exRNA play roles in endothelial permeability and inflammation via recognition by receptors such as VEGFR-2 (vascular endothelial growth factor receptor, receptor for advanced glycation end products (RAGE), and toll-like receptors (TLRs). Huang et al report that extracellular miR146a-5p activates TLR7 in macrophages and induces vascular permeability via TNFα. miR146a-5p is a miRNA that negatively regulates TLR signaling intracellularly by silencing IRAK1/TRAF6 expression. However, the extracellular form of miR146a-5p is vesicle-associated and is proinflammatory in macrophages. Thus, miR146a-5p fulfills the definition of a DAMP.