Role of protein tyrosine phosphatases in regulating the immune system: implications for chronic intestinal inflammation.

Abstract

Current hypothesis suggests that genetic, immunological, and bacterial factors contribute essentially to the pathogenesis of inflammatory bowel disease. Variations within the gene loci encoding protein tyrosine phosphatases (PTPs) have been associated with the onset of inflammatory bowel disease. PTPs modulate the activity of their substrates by dephosphorylation of tyrosine residues and are critical for the regulation of fundamental cellular signaling processes. Evidence emerges that expression levels of PTPN2, PTPN11, and PTPN22 are altered in actively inflamed intestinal tissue. PTPN2 seems to be critical for protecting intestinal epithelial barrier function, regulating innate and adaptive immune responses and finally for maintaining intestinal homeostasis. These observations have been confirmed in PTPN2 knockout mice in vivo. Those animals are clearly more susceptible to intestinal and systemic inflammation and feature alterations in innate and adaptive immune responses. PTPN22 controls inflammatory signaling in lymphocytes and mononuclear cells resulting in aberrant cytokine secretion pattern and autophagosome formation. PTPN22 deficiency in vivo results in more severe colitis demonstrating the relevance of PTPN22 for intestinal homeostasis in vivo. Of note, loss of PTPN22 promotes mitogen-activated protein kinase-induced cytokine secretion but limits secretion of nuclear factor κB-associated cytokines and autophagy in mononuclear cells. Loss of PTPN11 is also associated with increased colitis severity in vivo. In summary, dysfunction of those PTPs results in aberrant and uncontrolled immune responses that result in chronic inflammatory conditions. This way, it becomes more and more evident that dysfunction of PTPs displays an important factor in the pathogenesis of chronic intestinal inflammation, in particular inflammatory bowel disease.

• Authors: Marianne R Spalinger, Declan F McCole, Gerhard Rogler, Michael Scharl
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 21 Issue 3 Pg. 645-55 (Mar 2015) ISSN: 1536-4844 [Electronic] England
• PMID: 25581833 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Protein Tyrosine Phosphatases

Topics

• Animals
• Chronic Disease
• Humans
• Immune System (immunology)
• Inflammation (enzymology, immunology, pathology)
• Intestines (enzymology, immunology, pathology)
• Mice
• Protein Tyrosine Phosphatases (metabolism)