The plasticity and metabolic reprogramming of macrophage in ulcerative colitis

Macrophages exhibit phenotypic plasticity, which plays a role in driving tissue injury and promoting mucosal repair in ulcerative colitis (UC). Intestinal macrophages originate from both embryo-derived resident cells and circulating monocytes. Macrophage polarization influences inflammatory responses and is regulated by cytokines, chemokines, growth factors, and adhesion molecules. Tissue-specific metabolic reprogramming governs macrophage plasticity. Glucose metabolic reprogramming drives M1-like polarization. During glycolysis, mitochondria influence reactive oxygen species (ROS) production which alters the fate of macrophages in UC. Moreover, the communication of cell to cell can also regulate macrophage plasticity. Transcriptomics, proteomics, and single-cell sequencing can be employed to dissect the phenotypes and heterogeneity of macrophage polarization. Numerous clinical trials suggest that regulating macrophage polarization, inhibiting excessive activation of macrophages, blocking the abnormal recruitment of macrophages to intestinal inflammatory sites, macrophage-directed cell therapy, and combination therapy can effectively treat patients with UC. Indeed, the macrophage polarization is characterized by ROS, microbial community and bacterial products in inflammation of the colonic mucosa which is regulated by metabolic programming of macrophages. Indeed, macrophage polarization is characterized by ROS, microbial community, and bacterial products in the inflamed colonic mucosa. The macrophage polarization process is tightly regulated by the metabolic programming. In summary, this review analyzes macrophage plasticity and functional diversity, as well as the metabolic reprogramming and microenvironmental signals that shape macrophage polarization, and offers new insights for macrophage-based clinical interventions in UC.