Recently, a study demonstrated that the anti-TNF medication, adalimumab, restricted AIEC replication in CD macrophages by inducing Flotillin (FLOT-1) and restricting chitinase 3-like 1 proteins (CHI3L1), an AIEC receptor, in macrophages.46 In the current study, we have demonstrated for the first time how an IBD-susceptibility PTPN2 gene variant regulates a critical cell surface receptor to mediate AIEC colonization. Here, PTPN2 is linked to inflammatory bowel disease.