Neutrophil extracellular trap-mediated activation of endosomal toll-like receptors induce immune activation in juvenile-onset systemic lupus erythematosus

Introduction Juvenile-onset Systemic Lupus Erythematosus (JSLE) is a multisystem autoimmune disorder characterized by the overproduction of autoantibodies against nuclear selfantigens. Activated neutrophils may undergo cell death by NETosis, forming mesh-like structures termed Neutrophil extracellular traps (NETs). Comprising of DNA, histones and antimicrobial proteins, increasing evidence implicates NETs in many pathological conditions, including SLE. Toll like receptors (TLRs) are pattern recognition receptors capable of mediating immune responses. Endosomally localised TLR 7 and 9, expressed highly in JSLE, can detect nuclear antigens. Our hypothesis is that NETs offer a novel source of nuclear auto-antigens that are being detected via TLR 7/9, resulting in the downstream activation of the immune system.