The immunomodulatory effect and mechanism of a Chinese herbal formulation for the treatment of chronic colitis

Ulcerative colitis (UC) is a long-term inflammatory condition marked by a breakdown of immune tolerance to luminal antigens leading to progressive damage to intestinal tissue. Therefore, restoring immune tolerance is essential for controlling aberrant immune responses and UC progression. We discovered that a herbal formulation exhibits a potent inhibitory effect on murine models of chronic colitis. First, our study found that the therapeutic effect of the formulation is rooted in the increased de novo generation of lamina propria regulatory T cells. Further analysis demonstrates that the formulation promotes the accumulation and function of tolerogenic dendritic cells, which leads to an increase in the de novo generation of regulatory T cells in vivo. Mechanistically, the herbal formulation promoted the differentiation of tolerogenic dendritic cells by upregulating oxidative phosphorylation in these cells. Interference with the electron transport chain associated with oxidative phosphorylation reversed the phenotype of dendritic cells induced by the herbal formulation. In conclusion, our study demonstrates that the herbal formulation suppresses the progression of colitis primarily by establishing a tolerogenic microenvironment that favors colitis inhibition.