Yi Wenzhe, Sun Fang, Qian Xindi, Xu Xiaoxuan, Yan Dan, Zhao Zhiwen, Xu Leiming, Wang Dangge, Li Yaping
State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Adv Mater. 2025 Sep;37(35):e2420113. doi: 10.1002/adma.202420113. Epub 2025 Jun 22.
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 FasCD8 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.
炎症是肠道炎性疾病（如炎症性肠病，IBD）的关键驱动因素。虽然生物制剂在治疗部分患者方面已取得显著成效，但对于解决原发性和继发性无反应者，仍迫切需要其他治疗策略。在本研究中，一种基于树突状细胞（DC）的生物杂交免疫调节剂被开发出来以减轻肠道炎症，在对抗IBD方面显示出显著疗效。这种生物杂交免疫调节剂是通过将负载消退素E1的脂质体与Fas配体（FasL）转染的DCs偶联而构建的。在IBD患者的肠道组织样本中观察到Fas表达升高，并且该免疫调节剂通过选择性清除Fas⁺ CD8⁺ T细胞和中性粒细胞有效减轻了炎症。这种方法的治疗潜力在IBD的小鼠和兔子模型中均得到验证，在这些模型中它表现出显著的抗炎作用。此外，该免疫调节剂可以使用人外周血单核细胞和骨髓来源的DCs制造，显示出强大的诱导T细胞凋亡的能力。本研究提出了一种减轻肠道炎症的可行且可定制的策略，为IBD的治疗提供了有前景的进展。
