Regulation of epithelial barrier function by Crohn's disease associated gene PTPN2

Results Our data demonstrated a decrease in barrier integrity, as measured by TER, by IFN pre-treatment followed by addition of TNF on T84 cell monolayers. This reduction was significantly more dramatic than in controls (***, p<0.001) or T84 cell monolayers treated with IFNg alone (*, p<0.05). Furthermore, IFN pre-treatment followed by addition of TNF on T84 cell monolayers demonstrated an alteration in the distribution of claudin-2. PTPN2 showed enhanced expression, as well as a shift in distribution away from the nucleus after this treatment regime. Knockdown of the PTPN2 gene in T84 cell monolayers enhanced the cytokine induced changes as regards to TER. A trend towards increased paracellular permeability as measured by FITC-dextran flux was also observed in PTPN2 deficient T84 cell monolayers treated with IFN alone compared to controls. A higher expression of claudin-2 was observed while experimenting on T84 cell monolayers with repressed PTPN2 expression.