Citrullination is a posttranslational modification of
proteins mediated by a specific family of
enzymes called
peptidylarginine deiminases (PAD). Dysregulation of these
enzymes is involved in the etiology of various diseases, from
cancer to autoimmune disorders. In
inflammatory bowel disease (IBD), data for a role of citrullination in the disease process are starting to accumulate at different experimental levels including gene expression analyses,
RNA, and
protein quantifications. Most data have been generated in
ulcerative colitis, but data in
Crohn disease are lacking so far. In addition, the citrullination of
histones is the fundamental process promoting
inflammation through the formation of neutrophil extracellular traps (NETs). Interestingly, NETs have also been shown to activate fibroblasts into myofibroblasts in fibrotic
interstitial lung disease. Therefore, citrullination merits more thorough study in the bowel to determine its role in driving disease complications such as
fibrosis. In this review we describe the process of citrullination and the different players in this pathway, the role of citrullination in autoimmunity with a special focus on IBD, the emerging role for citrullination and NETs in triggering
fibrosis, and, finally, how this process could be therapeutically targeted.