Oral Regulatory T Cell-Derived Exosomes in the Treatment of Ulcerative Colitis

LI Xiaoyan^1,2, GAO Yuanyuan³, YE Yuqi², ZHANG Fan⁴, LI Meng²*, DING Feng¹, ZHANG Jin^1,2,3*

(¹College of Life and Geographic Sciences, Kashi University, Kashi 844000, China; ²College of Biological and Chemical Engineering, Jiaxing University, Jiaxing 314001, China; ³Jiaxing i-bio Biotechnology Co., Ltd, Jiaxing 314006, China; 4Longgang Central Hospital of Shenzhen, Shenzhen 518166, China)

Abstract:

This study aimed to evaluate the therapeutic effects of oral Treg-Exo (regulatory T cell-derived exosomes) on DSS (dextran sulfate sodium)-induced UC (ulcerative colitis) mice. To enhance resistance against gastric acid, Treg-Exo were coated with chitosan and sodium alginate, forming LBL (layer-by-layer) shell coared Treg-Exo@LBL. After oral administration, the targeting ability of Treg-Exo@LBL was analyzed using an IVIS imaging system. The therapeutic effect of Treg-Exo@LBL was evaluated via weight change, colon length, DAI score and H&E pathological section. The safety of Treg-Exo@LBL was evaluated by blood routine examination, biochemical index detection and histological staining of major organs. The results revealed that coating Treg-Exo with LBL increased they accumulation at UC sites, resulting in improved therapeutic outcomes. Compared to the Treg-Exo group, the Treg-Exo@LBL group exhibited an increase in colon length by approximately 0.58 cm, a 10% increase in body weight, and notable reductions in inflammatory markers IL-12, IL-6, and myeloperoxidase levels in colonic tissue. Safety evaluation results showed that the representative blood routine and biochemical indexes of mice were within the normal range after Treg-Exo@LBL intervention. Additionally, histological H&E staining of the major organs showed no abnormal changes, indicating the biosafety of Treg-Exo@LBL. In conclusion, Treg- Exo@LBL can serve as a safe agent which could target inflammatory bowel disease and treat UC effectively.

CSTR: 32200.14.cjcb.2025.05.0006