Dendritic Cell-Based Biohybrid Immunomodulator Alleviates Intestinal Inflammatory Disease.

Abstract

Inflammation is a key driver of intestinal inflammatory diseases, such as inflammatory bowel disease (IBD). While biologics have demonstrated notable success in treating some patients, there remains a critical need for alternative therapeutic strategies to address primary and secondary non-responders. In this study, a dendritic cell (DC)-based biohybrid immunomodulator is developed to alleviate intestinal inflammation, demonstrating remarkable efficacy in combating IBD. This biohybrid immunomodulator is engineered by conjugating resolvin E1-loaded liposomes with Fas ligand (FasL)-transfected DCs. Elevated Fas expression is observed in intestinal tissue samples from IBD patients, and the immunomodulator effectively reduced inflammation by selectively eliminating FasCD8T cells and neutrophils. The therapeutic potential of this approach is validated in both mouse and rabbit models of IBD, where it exhibites significant anti-inflammatory effects. Furthermore, the immunomodulator can be manufactured using human peripheral blood mononuclear cells and bone marrow-derived DCs, demonstrating a robust capacity to induce T cell apoptosis. This study presents a feasible and customizable strategy for mitigating intestinal inflammation, offering a promising advancement in the treatment of IBD.