Genome-wide association studies (GWAS) have identified >200 risk loci in Crohn’s disease and ulcerative colitis or as shared loci. Pathway analysis of these risk loci identified several variants in the Jak-STAT candidate network and of protein tyrosine phosphatase non-receptor type 2 (PTPN2, TC-PTP). PTPN2 dephosphorylates not only receptor protein tyrosine kinases but also non-receptor protein tyrosine kinases like JAK1, JAK2, JAK3, the Src family kinases, STAT3. In subepithelial myofibroblasts from strictured ileum of patient with fibrostenotic Crohn’s disease we identified a unique signaling pathway, of JAK-mediated STAT3(S727) and STAT3(Y705) phosphorylation regulated increased TGF-β1 expression and increased collagen I production.