The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang, China.
Jiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang, China.
Aging (Albany NY). 2023 Apr 4;15(14):6721-6735. 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.
本研究旨在探讨辅助性 T 细胞 1（Th1）在慢性结肠炎中的作用及其免疫调节机制。检测了炎症性肠病（IBD；溃疡性结肠炎+克罗恩病，UC+CD）患者组织中 Th1 和 Th2 的比例以及相关细胞因子的水平。采用 DSS 诱导 IBD 小鼠模型；诱导后，Th1 细胞被诱导并扩增，然后进行腹腔注射。观察小鼠的生活状态和体重变化，检测黏膜组织中 M1 巨噬细胞的比例和黏膜屏障损伤。用巨噬细胞清除剂（氯膦酸脂质体，CLL）处理后，观察 Th1 对 IBD 小鼠的影响。然后，将肠巨噬细胞与 Th1 共培养，观察 Th1 对肠巨噬细胞极化的影响。此外，用 STAT3 抑制剂处理细胞，进一步检测巨噬细胞的极化水平。然后将肠巨噬细胞与肠上皮细胞共培养，观察上皮细胞损伤程度。UC 和 CD 患者肠组织中的 Th1 比例高于健康对照者，但 Th2 比例的差异无统计学意义。在 IBD 小鼠模型中，Th1 诱导巨噬细胞 M1 极化，加重肠道炎症反应，导致黏膜屏障通透性增加。CLL 预处理拮抗 Th1 细胞的作用，减轻肠道组织炎症反应和黏膜屏障通透性。
