Open AccessDifferential regulation of JAK/STAT-signaling in patients with ulcerative colitis and Crohn’s disease
Author(s) -
Frederick C. Cordes,
Dirk Foell,
Nik Sheng Ding,
Georg Varga,
Dominik Bettenworth
Publication year - 2020
Publication title -
world journal of gastroenterology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.427
H-Index - 155
eISSN - 2219-2840
pISSN - 1007-9327
DOI - 10.3748/wjg.v26.i28.4055
Subject(s) - ulcerative colitis , crohn's disease , stat , medicine , jak stat signaling pathway , gastroenterology , disease , janus kinase , differential diagnosis , inflammatory bowel disease , signal transduction , immunology , cytokine , biology , pathology , receptor , stat3 , tyrosine kinase , genetics
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.