Therapeutic potential of Janus kinase inhibitors for the management of fibrosis in inflammatory bowel disease

Abstract Intestinal fibrosis in inflammatory bowel disease (IBD) is caused by uncontrolled accumulation of extracellular matrix deposited by fibroblasts. This may result in stricture formation, especially in Crohn's disease. Since there are no anti-fibrotic drugs available, endoscopic or surgical interventions are the only options to treat intestinal strictures. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway plays a crucial role in intestinal homeostasis and inflammation. JAK inhibition represents a relative novel therapeutic strategy in IBD by simultaneously blocking multiple cytokines across various inflammatory pathways. Interestingly, JAK inhibitors extend their benefits beyond anti-inflammatory effects, as they have been shown to interfere with fibrotic processes in various diseases, including IBD. We here summarize the current understanding of the role of the JAK-STAT pathway in the pathogenesis of intestinal fibrosis and the application of JAK inhibitors for IBD. In addition, we discuss the use of JAK inhibitors in other fibrotic-related diseases to postulate how these agents might be applied for future treatment of intestinal fibrosis.