PTGS2 and Cowden disease: Both COX2 and COX2-dependent prostaglandin E2 (PGE2) have been associated with maintaining adaptive immune tolerance to dietary antigens (255, 256), with COX2-total KO and COX2-myeloid specific KO mice shown to develop severe CD-like inflammation within the ileo-ceco-colic junctions significantly increasing intestinal permeability when fed a cholate-containing HFD (257, 258).