Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
J Dig Dis. 2011 Aug;12(4):286-94. doi: 10.1111/j.1751-2980.2011.00505.x.
Forkhead box P3 (FOXP3) plays an important role in the development and function of CD4(+) regulatory T (Treg) cells. In this study the percentage of CD4(+) FOXP3(+) Treg cells in peripheral blood mononuclear cells (PBMC) and the frequency of Treg cells in the colonic mucosa of patients with inflammatory bowel disease (IBD) were investigated.
The percentage of CD4(+) FOXP3(+) Treg cells in PBMC was analyzed by flow cytometry. Immunohistochemistry was used to examine the FOXP3(+) cells in the inflamed mucosa. Real-time polymerase chain reaction and Western blot were used to detect the expressions of FOXP3 mRNA and protein in PBMC and mucosal biopsy specimens of IBD patients, respectively.
Together with the decrease of percentage of Treg cells in PBMC, we found that the frequency of Treg cells increased significantly in inflamed mucosa of active or inactive Crohn's disease (CD) and ulcerative colitis (UC). The expressions of FOXP3 mRNA and protein increased in inflamed mucosa when compared with those in healthy controls, especially the FOXP3 mRNA in patients with active CD or UC. Interestingly, the expression of FOXP3 protein in active UC was higher than that in active CD.
There was a decrease of CD4(+) FOXP3(+) Treg cells in peripheral blood and an accumulation of Treg cells in inflamed mucosa. These data suggested that the suppressive function of Treg cells may be partially inhibited and this could be an important factor in the recurrence of disease, especially in UC.
叉头框 P3(FOXP3)在 CD4+调节性 T(Treg)细胞的发育和功能中发挥重要作用。本研究调查了炎症性肠病(IBD)患者外周血单个核细胞(PBMC)中 CD4+FOXP3+Treg 细胞的百分比和结肠黏膜中 Treg 细胞的频率。
通过流式细胞术分析 PBMC 中 CD4+FOXP3+Treg 细胞的百分比。免疫组织化学用于检测炎症黏膜中的 FOXP3+细胞。实时聚合酶链反应和 Western blot 分别用于检测 PBMC 和 IBD 患者黏膜活检标本中 FOXP3 mRNA 和蛋白的表达。
随着 PBMC 中 Treg 细胞百分比的降低,我们发现活动期或缓解期克罗恩病(CD)和溃疡性结肠炎(UC)患者的炎症黏膜中 Treg 细胞的频率显著增加。与健康对照相比,炎症黏膜中 FOXP3 mRNA 和蛋白的表达增加,尤其是活动期 UC 患者的 FOXP3 mRNA。有趣的是,活动期 UC 患者的 FOXP3 蛋白表达高于活动期 CD。
外周血中 CD4+FOXP3+Treg 细胞减少,炎症黏膜中 Treg 细胞积聚。这些数据表明 Treg 细胞的抑制功能可能部分受到抑制,这可能是疾病复发的一个重要因素,尤其是在 UC 中。