Dendritic Cell-Based Biohybrid Immunomodulator Alleviates Intestinal Inflammatory Disease

  • Adv Mater. 2025 Jun 22:e2420113. doi: 10.1002/adma.202420113.
Wenzhe Yi  1  2 ,  Fang Sun  3 ,  Xindi Qian  1 ,  Xiaoxuan Xu  1  2 ,  Dan Yan  1 ,  Zhiwen Zhao  1  2 ,  Leiming Xu  3 ,  Dangge Wang  4 ,  Yaping Li  1  2  5
Affiliations
  • 1. State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • 2. University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 3. Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China.
  • 4. Precision Research Center for Refractory Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
  • 5. Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, 264000, China.
PMID: 40545797 DOI: 10.1002/adma.202420113
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 Fas+CD8+ T 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.

Keywords
dendritic cells; fas/fas legend interaction; inflammatory bowel disease; liposomes.
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