Published online Jan 21, 2016. doi: 10.3748/wjg.v22.i3.1034
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.
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.