IsoalloLCA-intervened regulatory T cell exosomes alleviate inflammatory bowel disease by inhibiting NF-κB-associated inflammation in intestinal epithelial cells

Abstract

Regulatory T cells (Tregs) are the principal immune cells that exert anti-inflammatory effects within the organism. Their exosomes exhibit therapeutic efficacy across a broad spectrum of diseases owing to their high stability, low immunogenicity, and substantial penetration capacity. Recent research have indicated that isoallolithocholic acid (isoalloLCA), a metabolite associated with bile acid metabolism, may enhance Treg activity by upregulating forkhead box protein3 (Foxp3) expression. Hence, metabolite-based strategies for reinforcing Tregs may offer novel intervention options for treating related diseases. In this study, tumor necrosis factor (TNF)-α and dextran sulfate sodium (DSS) were employed to establish cellular and animal models of inflammatory bowel disease (IBD), further evaluating the therapeutic efficacy of isoalloLCA-intervened regulatory T cell exosomes (isoalloLCA-Exo) within this model. Our findings demonstrated that isoalloLCA-Exo effectively inhibit colitis progression in a murine model, as indicated by reduced inflammation, decreased apoptosis of intestinal epithelial cells, and improved intestinal barrier function. Furthermore, in vitro analyses elucidated the molecular mechanisms underlying the anti-inflammatory effects of isoalloLCA-Exo, revealing that the intervention effectively reversed TNF-α-induced inflammation and apoptosis in intestinal epithelial cells by modulating the NF-κB pathway. In conclusion, isoalloLCA-Exo can decelerate inflammatory bowel disease progression and suppress inflammatory response in intestinal epithelial cells by inhibiting NF-κB pathway. Notably, isoalloLCA-Exo exhibit superior efficacy to the traditional drug mesalazine and conventional treg exosome(NC-Exo). These findings have significant implications for optimizing Treg-derived exosome-based therapies for inflammation-related diseases.