结肠组织中Th1/Th2和Th17细胞失衡与溃疡性结肠炎的关系

摘要

目的 探讨结肠组织中Th1、Th2和Th17细胞失衡与溃疡性结肠炎(UC)的关系.方法 收集41例UC患者和52例对照者肠组织,采用反转录实时定量PCR检测结肠组织Thl、Th2和Thl7细胞相关转录因子(T-bet、GATA-3、RORγt)及细胞因子(IFN-γ、1L-4、IL-17A)mRNA水平;同时采用免疫组化检测结肠组织IFN-γ、IL-4、IL-17A的表达水平.结果 与对照组相比,UC患者结肠组织中GATA-3、RORγt和IL-17A mRNA水平明显提高(0.84±0.24 vs.0.69±0.22,P＜0.01;0.99±0.29 vs.0.83±0.23,P＜0.01;1.59±0.65 vs.1.35±0.43,P＜0.05).依据《改良Truelove和Witts 严重程度分型标准》将UC患者分层,与轻度患者相比,中重度患者结肠组织中GATA-3、RORγt和IL-17A mRNA水平明显升高(0.90±0.18 vs.0.78±0.16,P＜0.05;1.11±0.31 vs.0.87±0.26,P＜0.05;1.83±0.64 vs.1.34±0.66,P＜0.05).对UC患者肠组织行免疫组化检测显示,IL-17A阳性细胞主要位于结肠上皮细胞层和黏膜固有层;UC患者结肠组织中IL-17A的平均积分光密度值明显高于对照组(0.25±0.07 vs.0.13±0.03,P＜0.01),并且中重度患者明显高于轻度患者(0.31±0.07vs.0.19±0.06,P＜0.01).与对照组相比,UC患者结肠组织中GATA-3/T-bet、RORγt/T-bet和RORγt/GATA-3的mRNA比值均明显升高(1.12±0.30 vs.0.96±0.31,P＜0.05;1.33±0.37 vs.1.15±0.33,P＜0.05;1.44±0.45 vs.1.20±0.42,P＜0.01),并且中重度患者明显高于轻度患者(1.27±0.35 vs.1.00±0.32,P＜0.01;1.45±0.37 vs.1.19±0.36,P＜0.05;1.59±0.43 vs.1.28±0.46,P＜0.05).结论 Th1、Th2和Thl7细胞失衡可能与UC密切相关.%Objects To explore the association of ulcerative colitis (UC) with the imbalance between Th1,Th 2 and Th17 cells in the colonic tissues.Methods A total of 41 UC patients and 52 controls was recruited in the present study.The real-time fluorescent quantitative PCR was applied for detecting the mRNA levels of Thl,Th2 and Th 17 cells-associated transcription factors T-bet,GATA-3 and RORγt and cytokines IFN-γ,IL-4 and IL-17A in the colonic tissues.Simultaneously,the expressions of IFN-γ,IL-4 and IL-17A in the colonic tissues were also examined by an immunohistochemical staining method.Results Compared with the controls,the mRNA expressions of GATA-3,RORγt and IL-17A were more significantly enhanced in UC patients (0.84 ± 0.24 vs.0.69 ± 0.22,P=0.002;0.99 ± 0.29 vs.0.83 ± 0.23,P=0.004;1.59 ± 0.65 vs.1.35 ± 0.43,P=0.035).According to the ＂Truelove and Witts Severity Index＂,those patients were divided into different subgroups.The mRNA expressions of GATA-3,RORγt,and IL-17A were shown to be higher in patients with moderate and severe UC than in those with mild UC (0.90 ± 0.18 vs.0.78 ± 0.16,P=0.030;1.11 ± 0.31 vs.0.87 ± 0.26,P=0.011;1.83 ± 0.64 vs.1.34 ± 0.66,P=0.020).Moreover,the immunohistochemistry results demonstrated that the IL-17A positive cells were positioned mainly in the intestinal epithelial layer and lamina propria.Compared to the controls,the mean integral optic density of IL-17A was significantly increased in the colonic tissues of UC patients (0.25 ± 0.07 vs.0.13 ± 0.03,P＜0.001).The similar results were obtained for IL-17A in patients with moderate and severe UC when compared to those with mild UC (0.31 ± 0.07 vs.0.19 ± 0.06,P＜0.001).In contrast to the controls,the mRNA ratios ofGATA-3/T-bet,RORγt/ T-bet and RORγt/GATA-3 were significantly higher in the tissues of colonic UC patients (1.12 ± 0.30 vs.0.96 ± 0.31,P=0.014;1.33 ± 0.37 vs.1.15 ± 0.33,P=0.015;1.44 ± 0.45 vs.1.20 ± 0.42,P=0.009),and in the patients,the mRNA ratios for GATA-3/T-bet,RORγt/T-bet and RORγt/GATA-3 were significantly higher in the patients with moderate and severe UC than in those with mild UC (1.27 ± 0.35 vs.1.00 ± 0.32,P＜0.001;1.45 ± 0.37 vs.1.19 ± 0.36,P=0.028;1.59 ± 0.43 vs.1.28 ± 0.46,P=0.031).Conclusions These findings suggest that the imbalance between Thl,Th2 and Th17 cells in the colonic tissues may be implicated in UC.