Neutrophils can release their DNA as neutrophil extracellular traps (NETs) via a programmed cell death known as NETosis; this process is dependent on peptidyl arginine deiminase-4 (PAD4, aka Padi4) activity to facilitate the rapid de-condensation of chromatin into NETs. We envision that the formation of NETs would be an appropriate immune response in the gut, which is continuously exposed to trillions of bacteria. To test this hypothesis, we employed the NETs-deficient Pad4KO mice and their WT littermates in two well-established models of murine colitis, i.e., loss of IL-10 signaling (immune hyperactivation) and chemical-induced injury (DSS).