Accepted_test

Low-grade inflammation is typical for patients with inflammatory bowel disease in remission. Although numerous works have investigated the mechanisms underlying the regulation of gut barrier function using models of acute inflammation, there is still a lack of understanding about how the barrier function of the intestine is compromised during the development of low-grade inflammation.
We utilized Muc2-KO mice as a model of chronic colitis to study intestinal barrier in low-grade inflammation. In this model, actin filament structure and dynamics in the gut epithelium is disrupted, what is accompanied by Claudin 7 and beta-catenin delocalization from tight and adherence junctions, respectivelly. It was illustrated that in wild type mice the destabilization of microfilaments triggers an increase in epithelial barrier permeability due to delocalization of tight and adhesive junction proteins from the cell membrane. Apparently, similar mechanism underlies barrier dysfunction of the Muc2-KO mice. We expanded the results with two more mouse models of colitis: DSS-induced chronic colitis and CD4⁺CD45RB^High cell transfer model. They demonstrated similar phenotype with Muc2-KO mice indicating that disruption of intercellular contacts in the bowel epithelium due to F-actin destabilization may be universal mechanism for intestinal barrier disturbance in low-grade inflammation.