TNFAIP3 Maintains Intestinal Barrier Function and Supports Epithelial Cell Tight Junctions

摘要: Tight junctions between intestinal epithelial cells mediate the permeability of barrier, and loss barrier function mediated by TNF signaling is associated with inflammatory pathophysiology observed in Crohn's disease celiac disease. Thus, factors that modulate cell response to may be critical for maintenance function. alpha-induced protein 3 (TNFAIP3) a cytosolic acts negative feedback loop regulate induced Toll-like receptor ligands TNF, suggesting TNFAIP3 play role regulating barrier. To investigate specific we assessed TNFAIP3−/− mice LPS-treated villin-TNFAIP3 transgenic mice. had greater compared wild-type littermates, while were protected from increases seen within indicating controlled TNFAIP3. In cultured human lines, expression regulated both TNF-induced myosin light chain kinase-regulated tight junction dynamics but did not affect kinase activity. Immunohistochemistry mouse intestine revealed inhibits LPS-induced occludin apical border epithelium. We also found deubiquitinates polyubiquitinated occludin. These vivo vitro studies support promoting integrity demonstrate its novel ability maintain homeostasis through regulation.