Loss-of-function mutations in the protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene locus increase IBD susceptibility. We reported that PTPN2 knockdown (PTPN2-KD) in intestinal epithelial cells (IECs): (i) increased IFN-g activation of STAT signaling; (ii) reduced IEC barrier function; (iii) increased expression of the tight junction (TJ) protein, claudin-2, by IFN-g; and that the claudin-2 promoter contains a STAT binding sequence. Increased claudin-2 expression occurs in IBD and increases permeability to cations thus reducing transepithelial electrical resistance (TER).