Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2020; 26(28): 4055-4075
Published online Jul 28, 2020. doi: 10.3748/wjg.v26.i28.4055
Differential regulation of JAK/STAT-signaling in patients with ulcerative colitis and Crohn’s disease
Friederike Cordes, Dirk Foell, John Nik Ding, Georg Varga, Dominik Bettenworth
Friederike Cordes, Dominik Bettenworth, Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, Münster D-48149, Germany
Dirk Foell, Georg Varga, Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster, Münster D-48149, Germany
John Nik Ding, Department of Gastroenterology, St. Vincent’s Hospital, Melbourne 3002, Australia
John Nik Ding, Department of Medicine, University of Melbourne, East Melbourne 3002, Australia
Author contributions: Cordes F designed and wrote the review, performed the literature research and interpretation and wrote the manuscript; Bettenworth D contributed to the review design, literature research, manuscript writing and supervised the review; Varga G and Foell D contributed to manuscript writing, literature research and final revision of the manuscript; Ding JN contributed to manuscript writing and final revision of the manuscript.
Conflict-of-interest statement: Bettenworth D is on the advisory board or a consultant for Amgen, AbbVie, Dr. Falk Foundation, Ferring, MSD, Pfizer, Pharmacosmos, Roche, Takeda, Tillotts Pharma and Vifor. Ding JN is on the advisory board or delivered talks for Abbvie, Janssen, and Pfizer. None of the authors has received fees for serving as a speaker or received research funding with regard to this study. None of the authors own stocks and/or shares with regards to this study. None of the authors own patents with regard to this study.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Friederike Cordes, MD, Doctor, Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, Albert-Schweitzer-Campus 1, Münster D-48149, Germany.
Received: February 3, 2020
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
Core Tip

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.