Conclusion
Our study suggests that DNMT3a induces enterocyte barrier dysfunction to aggravate UC progression via TNFSF13-mediated interaction of enterocyte and B cells.
Objective
Dysfunction of the enterocyte barrier is associated with the development of ulcerative colitis (UC). This study was aimed at exploring the effect of DNMT3a on enterocyte barrier function in the progression of UC and the underlying mechanism. Method: Mice were given 3.5% dextran sodium sulphate (DSS) in drinking water to induce colitis. The primary intestinal epithelial cells (IECs) were isolated and treated with lipopolysaccharide (LPS) to establish an in vitro inflammatory model. We detected mouse clinical symptoms, histopathological damage, enterocyte barrier function, B cell differentiation, DNA methylation level, and cytokine production. Subsequently, the effect of DNMT3a from IECs on B cell differentiation was explored by a cocultural experiment. Result: DSS treatment significantly reduced the body weight and colonic length, increased disease activity index (DAI), and aggravated histopathological damage. In addition, DSS treatment induced downregulation of tight junction (TJ) protein, anti-inflammatory cytokines (IL-10 and TGF-β), and the number of anti-inflammatory B cells (CD1d+) in intestinal epithelial tissues, while upregulated proinflammatory cytokines (IL-6 and TNF-α), proinflammatory B cells (CD138+), and DNA methylation level. Further in vitro