Importantly, NETs have been shown to initiate fibroblast activation and collagen deposition via the TLR2/NF-κB pathway in CD, while neutrophil-specific PAD4 deletion attenuates intestinal fibrosis in chronic DSS colitis, supporting PAD4 inhibition as a dual anti-inflammatory and anti-fibrotic strategy in IBD [238]. This evidence concerns the gene NFKB1 and irritable bowel syndrome.