Th1 promotes M1 polarization of intestinal macrophages to regulate colitis-related mucosal barrier damage

• Published in: Aging (Albany, NY.) NY.), 2023-04, Vol.15 (14), p.6721-6735
• Main Authors: Ruan, Shuiliang, Xu, Liang, Sheng, Yongjia, Wang, Jin, Zhou, Xiaohong, Zhang, Caiqun, Guo, Li, Li, Wenyan, Han, Chenyang
• Format: Article
• Language: English
• Subjects: Animals; Colitis - chemically induced; Disease Models, Animal; Inflammatory Bowel Diseases; Intestinal Mucosa; Leukemia, Lymphocytic, Chronic, B-Cell; Macrophages; Mice; Research Paper
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.204629

This work aimed to investigate the role of helper T cell 1 (Th1) in chronic colitis and its immunoregulatory mechanism. The proportions of Th1 and Th2, and the levels of related cytokines in tissues from patients with inflammatory bowel disease (IBD; ulcerative colitis+Crohn's disease, UC+CD) were detected. DSS was used to induce the mouse model of IBD; thereafter, Th1 cells were induced and amplified before they were injected intraperitoneally. Later, the changes in life state and body weight of mice were observed, the proportion of M1 macrophages in mucosal tissues and mucosal barrier damage were detected. After treatment with macrophage scavenging agent (Clodronate Liposomes, CLL), the influence of Th1 on IBD mice was observed. Then, the intestinal macrophages were co-cultured with Th1 to observe the influence of Th1 on the polarization of intestinal macrophages. Besides, cells were treated with the STAT3 inhibitor to further detect the macrophage polarization level. Intestinal macrophages were later co-cultured with intestinal epithelial cells to observe the degree of epithelial cell injury. The Th1 proportions in intestinal tissues of UC and CD patients were higher than those in healthy subjects, but the difference in Th2 proportion was not significant. In the IBD mouse model, Th1 induced the M1 polarization of macrophages, aggravated the intestinal inflammatory response, and resulted in the increased mucosal barrier permeability. Pretreatment with CLL antagonized the effect of Th1 cells, reduced the intestinal tissue inflammatory response and mucosal barrier permeability.