Figure 7.

Neutrophil extracellular traps (NETs) exacerbate mouse experimental colitis by impairing intestinal barrier function. (Left) NETs are abundant in the colon of mouse in DSS-induced or TNBS-induced colitis models. In the colon of non-treated mouse, aberrant NET formation promotes the apoptosis of intestinal cells during colitis. NETs also alter intestinal epithelial permeability leading to luminal bacterial translocation into the colon and MLN as well as gut inflammation in vivo. Mechanistically, histones are the major protein components of NET structure that decrease the intestinal barrier integrity and function, as well as promotes the cytotoxicity of intestinal epithelial cells. (Right) Disruption of NET structure with DNase I in mice with DSS-induced or TNBS-induced colitis protects the host from intestinal inflammation and injury by restoring the intestinal barrier integrity and function that prevent luminal bacterial translocation into the colon and MLN, suggesting that NETs play a distinct role that is required for the development and pathogenesis of colitis.