Published online Jul 28, 2020. doi: 10.3748/wjg.v26.i28.4055
Peer-review started: February 3, 2020
First decision: February 27, 2020
Revised: May 24, 2020
Accepted: June 18, 2020
Article in press: June 18, 2020
Published online: July 28, 2020
In 2018, the pan-Janus kinase (JAK) inhibitor tofacitinib was launched for the treatment of ulcerative colitis (UC). Although tofacitinib has proven efficacious in patients with active UC, it failed in patients with Crohn’s disease (CD). This finding strongly hints at a different contribution of JAK signaling in both entities. Here, we review the current knowledge on the interplay between the JAK/signal transducer and activator of transcription (STAT) pathway and inflammatory bowel diseases (IBD). In particular, we provide a detailed overview of the differences and similarities of JAK/STAT-signaling in UC and CD, highlight the impact of the JAK/STAT pathway in experimental colitis models and summarize the published evidence on JAK/STAT-signaling in immune cells of IBD as well as the genetic association between the JAK/STAT pathway and IBD. Finally, we describe novel treatment strategies targeting JAK/STAT inhibition in UC and CD and comment on the limitations and challenges of the new drug class.
Core tip: The pan-Janus kinase (JAK)-inhibitor tofacitinib is efficacious in patients with active ulcerative colitis (UC) but not Crohn’s disease (CD), which hints at different contributions of JAK-signaling in both entities. In this review, available data on differential JAK/signal transducer and activator of transcription (STAT)-signaling in UC and CD were analyzed. The literature review identified differential cell-subset specific JAK/STAT-signaling including increased T-cell-associated STAT1 signaling in CD and STAT6 signaling in UC, while in myeloid cells inflammatory STAT1 was increased in UC compared with CD indicating a less inflammatory role of myeloid cells in CD. Development of JAK/STAT-inhibitors with specific targeting of associated inflammatory pathways might further improve the efficacy and safety profiles of this drug class.