γδT细胞通过IL-17调控TGF-β/Smad信号通路促进CD小鼠肠纤维化OA
γδT cells promote intestinal fibrosis in CD mice by regulating the TGF-β/Smad signaling pathway through IL-17
目的:基于克罗恩病(Crohn's disease,CD)肠纤维化模型探讨 γδT 细胞通过白细胞介素-17(IL-17)调控转化生长因子-β(TGF-β)/Smad信号通路对肠纤维化的作用及机制研究.方法:雄性BALB/c小鼠28只,随机分为对照组,模型组、抗IL-17A抗体干预组、抗TCR γ/δ抗体干预组.采用TNBS/50％酒精灌肠构建CD肠纤维化模型,注射相应抗体.记录小鼠体重,疾病活动度指数(DAI),第7周处死小鼠后取结肠组织并测量其长度.H&E染色观察结肠组织形态结构变化;Masson染色观察结肠组织中胶原蛋白;免疫组化检测α-平滑肌肌动蛋白(α-SMA)的表达;ELISA检测IL-17、TGF-β、干扰素-γ(IFN-γ)和IL-10的表达水平;Western blot 检测 α-SMA、结缔组织生长因子(CTGF)、Ⅰ型胶原(Collagen Ⅰ)、Collagen Ⅲ及TGF-β/Smad信号通路相关蛋白.结果:与对照组相比,模型组DAI评分升高,结肠长度缩短;病理显示结肠组织损伤严重,Masson染色可见大量蓝染的胶原纤维;IFN-γ、IL-10表达下降,IL-17、TGF-β、α-SMA、CTGF、Collagen Ⅰ、Collagen Ⅲ、TGF-β1、Smad2/3、p-Smad2/3表达明显升高(P<0.05).与模型组相比,给予抗IL-17A抗体或抗TCR γ/δ抗体处理后,明显抑制小鼠TNBS诱导的各项指标变化(P<0.05),减轻肠道纤维化.结论:γδT 细胞能促进肠道纤维化,作用机制可能与激活相关IL-17信号通路有关.
Objective:To investigate the role and mechanism of γδT cells regulating the transforming growth factor-β(TGF-β)/Smad signaling pathway through interleukin-17(IL-17)in intestinal fibrosis,based on the Crohn's disease(CD)intesti-nal fibrosis model.Methods:A total of twenty-eight male BALB/c mice were randomly picked out.Thereafter,these mice were classified into four separate groups:the control group,the model group,the anti-IL-17A antibody intervention group,and the anti-TCR γ/δ antibody intervention group.Construct a CD intestinal fibrosis model using TNBS/50％alcohol enema and inject corresponding antibodies.Record the weight and disease activity index(DAI)of mice,and after euthanizing the mice in the 7th week,take colon tissue and measure its length.H&E staining was used to observe changes in tissue morphology and structure;Masson staining was used to observe collagen in colon tissue;Immunohistochemical detection of the expression of α-smooth mus-cle actin(α-SMA);ELISA was used to detect the expression levels of IL-17,TGF-β,interferon-γ(IFN-γ),and IL-10;West-ern blot was used to detect α-SMA,connective tissue growth factor(CTGF),type Ⅰ collagen(Collagen Ⅰ),Collagen Ⅲ,and TGF-β/Smad signaling pathway related proteins.Results:Compared to the control group,the model group showed an increase in DAI score and a reduction in colon length;Pathological examination showed severe damage to the colon tissue,and Masson stain-ing revealed a large number of blue stained collagen fibers;The expression of IFN-γ and IL-10 decreased,while the expression of IL-17,TGF-β,α-SMA,CTGF,Collagen Ⅰ,Collagen Ⅲ,TGF-β1,Smad2/3,and p-Smad2/3 showed a significant increase(P<0.05).However,in comparison to the model group,treatment with anti-IL-17A antibody or anti TCR γ/δ antibody signifi-cantly inhibited the changes in various indicators induced by TNBS in mice(P<0.05)and alleviated intestinal fibrosis.Conclu-sion:Gamma delta T cells can promote intestinal fibrosis,and the mechanism of action may be related to the activation of the IL-17 signaling pathway.
李永荣;陈名利;曾祖妮;陈超超;何周桃;蓝程
海南医科大学附属海南医院/海南省人民医院消化内科,海南 海口 570311海南医科大学附属海南医院/海南省人民医院消化内科,海南 海口 570311海南医科大学附属海南医院/海南省人民医院消化内科,海南 海口 570311海南医科大学附属海南医院/海南省人民医院消化内科,海南 海口 570311海南医科大学附属海南医院/海南省人民医院消化内科,海南 海口 570311海南医科大学附属海南医院/海南省人民医院消化内科,海南 海口 570311
医药卫生
克罗恩病(CD)肠道纤维化γδT细胞IL-17
Crohn's disease(CD)IntestineFibrosisγδT T cellsIL-17
《海南医科大学学报》 2026 (12)
881-889,9
This study was supported by the National Natural Science Foundation of China(81860102,82060102)High-Level Talent Program of Natural Science Foundation of Hainan Province(821RC1116) 国家自然科学基金(81860102,82060102)海南省自然科学基金高层次人才项目(821RC1116)
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