Hassan SW, Doody KM, Hardy S et al. PLoS One 2010;5:e8868.
The authors of this study investigated the possible role of protein tyrosine-protein phosphatase non-receptor type 2(PTPN2) in IBD using heterozygous PTPN2 mice in a dextran sulfate sodium (DSS)-induced colitis model. In comparison with wild-type group, the mice with a single copy of the PTPN2 gene were more susceptible to DSS-induced inflammation suggesting a potential role for PTPN2 as a regulator of inflammatory response in IBD.
Following the successes of genome-wide association studies (GWAS) in identifying genes/variants associated with IBD, studies to investigate the biological significance of the implicated genes or variants are now forthcoming. T cell protein tyrosine phosphatase/protein tyrosine-protein phosphatase non-receptor type 2 (TC-PTP/PTPN2) gene is one such gene located in the region of chromosome 18p11 that was identified by the Wellcome Trust Case Control Consortium analysis in 2007 [1]. PTPN2 encodes an enzyme that is essential for the proper functioning of the immune system and participates in the control of cell proliferation and inflammation. PTPN2–/– mice display various immunodeficiencies, with hypersensitivity to lipopolysaccharide (LPS), and die within 3 weeks of birth due to anemia and widespread inflammation [2]. Hassan and colleagues show that Balb/c heterozygous PTPN2 heterozygous (PTPN2+/–) mice develop more severe colitis and weight loss when challenged with 5% dextran-sulfate sodium (DSS), compared with DSS-challenged control mice. Upregulation of colonic mRNA transcripts for interleukin-6 (IL-6), IL-23, 1L-12b, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) was observed with increased serum IL-6 levels. Another recent study showed that PTPN2 may be involved in the maintenance of epithelial barrier function. Scharl et al. showed that in vitro, PTPN2 is activated by IFN-γ and limits subsequent IFN-γ signaling and its associated negative effects on epithelial barrier function [3]. The present study by Hassan et al. suggests that PTPN2 may be important in the prevention of DSS-induced colitis. However, more detailed studies into the underlying mechanism are required. The use of intestine-specific PTPN2 knock-out models will facilitate such analyses.