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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2016; 22(3): 1034-1044
Published online Jan 21, 2016. doi: 10.3748/wjg.v22.i3.1034
Protein tyrosine phosphatase non-receptor type 2 and inflammatory bowel disease
Marianne R Spalinger, Declan F McCole, Gerhard Rogler, Michael Scharl
Marianne R Spalinger, Gerhard Rogler, Michael Scharl, Division of Gastroenterology and Hepatology, University Hospital Zurich, 8091 Zurich, Switzerland
Declan F McCole, Division of Biomedical Sciences, University of California, Riverside (UCR), Riverside, CA 92521, United States
Gerhard Rogler, Michael Scharl, Zurich Center for Integrative Human Physiology, University of Zurich, 8091 Zurich, Switzerland
Author contributions: Spalinger MR, McCole DF, Rogler G and Scharl M solely contributed to this paper.
Supported by Grants from the Swiss National Science Foundation (SNF) to MS, Grant No. 314730-146204 and No. CRSII3_154488/1 (to Rogler G), Grant No. 310030-120312; and the Swiss IBD Cohort, Grant No. 3347CO-108792.
Conflict-of-interest statement: The authors have no conflict of interests to disclose.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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:
Correspondence to: Michael Scharl, MD, Division of Gastroenterology and Hepatology, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.
Telephone: +41-44-2559519 Fax: +41-44-2559497
Received: April 21, 2015
Peer-review started: April 23, 2015
First decision: July 20, 2015
Revised: August 31, 2015
Accepted: November 19, 2015
Article in press: November 19, 2015
Published online: January 21, 2016

Genome wide association studies have associated single nucleotide polymorphisms within the gene locus encoding protein tyrosine phosphatase non-receptor type 2 (PTPN2) with the onset of inflammatory bowel disease (IBD) and other inflammatory disorders. Expression of PTPN2 is enhanced in actively inflamed intestinal tissue featuring a marked up-regulation in intestinal epithelial cells. PTPN2 deficient mice suffer from severe intestinal and systemic inflammation and display aberrant innate and adaptive immune responses. In particular, PTPN2 is involved in the regulation of inflammatory signalling cascades, and critical for protecting intestinal epithelial barrier function, regulating innate and adaptive immune responses, and finally for maintaining intestinal homeostasis. On one hand, dysfunction of PTPN2 has drastic effects on innate host defence mechanisms, including increased secretion of pro-inflammatory cytokines, limited autophagosome formation in response to invading pathogens, and disruption of the intestinal epithelial barrier. On the other hand, PTPN2 function is crucial for controlling adaptive immune functions, by regulating T cell proliferation and differentiation as well as maintaining T cell tolerance. In this way, dysfunction of PTPN2 contributes to the manifestation of IBD. The aim of this review is to present an overview of recent findings on the role of PTPN2 in intestinal homeostasis and the impact of dysfunctional PTPN2 on intestinal inflammation.

Keywords: Protein tyrosine phosphatase non-receptor type 2, Inflammatory bowel disease, Chronic intestinal inflammation, Barrier function, Phosphorylation

Core tip: Genetic variants and subsequently aberrant function of protein tyrosine phosphatase non-receptor type 2 (PTPN2) have been associated with inflammatory bowel disease (IBD). Protein levels of PTPN2 are increased in the mucosa of IBD patients and PTPN2-deficient mice suffer from severe intestinal as well as systemic inflammation and feature alterations in innate and adaptive immune responses. In the innate immune system, dysfunction of PTPN2 results in increased secretion of pro-inflammatory cytokines, impairs autophagosome formation, and mediates disruption of epithelial barrier function. In the adaptive immune system, PTPN2 is involved in controlling T-cell proliferation, differentiation and promoting T-cell tolerance. Consequently, variants in PTPN2 importantly affect intestinal homeostasis and contribute to IBD pathogenesis.