deficiency reduces susceptibility to colitis by enhancing intestinal barrier function and suppressing inflammation.

INTRODUCTION

has been identified as a susceptible gene for inflammatory bowel diseases (IBD). However, the function of in normal development and IBD pathogenesis remains unknown.

METHODS

We administered drinking water with 3% dextran sodium sulfate (DSS) to wild-type (WT) and knockout (KO) mice for seven consecutive days to induce IBD. Subsequently, we further examined whether KO affects intestinal barrier and inflammation.

RESULTS

We demonstrated that deficiency partially protects mice from DSS-induced IBD, even though no obvious phenotypes were observed in KO mice. deletion leads to strengthened tight junctions between intestinal epithelial cells, elevated intestinal stem cell activity, and enhanced mucus layer. All these three mechanisms work together to improve the intestinal barrier integrity in KO mice. In addition, deficiency mitigates inflammation by reducing the expression of IL-1β and IL-6 by macrophages.

DISCUSSION

Our studies validate the crucial role of in IBD pathogenesis, and reveal that deficiency may ameliorate DSS-induced IBD through improving the intestinal barrier integrity, as well as suppressing inflammatory response mediated by macrophages. These findings suggest that could be a promising therapeutic target for the treatment of IBD.