Immune dysregulation in ulcerative colitis: pathogenic mechanisms and therapeutic strategies of traditional Chinese medicine.

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized primarily by immune dysregulation. Its pathogenesis involves multiple factors, including dysregulation of T-cell subsets, hypersecretion of pro-inflammatory cytokines, imbalance in the gut microbiota, and disruption of the intestinal barrier. Among T-cell subsets, abnormal activation of Th1 and Th17 cells, in conjunction with Treg dysfunction, significantly amplifies local pro-inflammatory signals. Pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-17, exacerbate apoptosis and disrupt tight junctions (TJs) in intestinal epithelial cells (IECs), thereby creating favorable conditions for invasion by pathogenic bacteria and their metabolites. Intestinal microecological imbalance not only leads to significant alterations in the structure of the bacterial flora but also involves abnormal fluctuations in its metabolites that directly regulate intestinal immune homeostasis, a factor closely associated with the severity of inflammation and prognosis of ulcerative colitis. Recent studies have demonstrated that in the treatment of UC, traditional Chinese medicine (TCM) achieves a multi-target, multi-pathway integrated intervention by regulating immune cell differentiation, balancing inflammatory factor levels, repairing the intestinal epithelial barrier, and remodeling the structure of the bacterial flora. This article reviews the pathogenic mechanisms underlying immune dysregulation in UC and the advances in research on TCM's role in immune regulation, anti-inflammatory repair, and flora modulation, encompassing the mechanisms of action of individual active ingredients and classic TCM compound formulas. Although some studies have preliminarily confirmed TCM's potential to modulate immunity and repair the intestinal barrier, breakthroughs in mechanism analysis, herb standardization, and large-scale validation remain forthcoming. It is anticipated that the unique advantages of TCM will be translated into a more precise therapeutic strategy for UC through modern molecular and systems biology approaches.