γδT细胞在实验性自身免疫性肝炎中的表达及意义  

Expression and significance of γδT cells in experimental autoimmune hepatitis

作　　者：秦刚[1] 沈毅[2] 化雨 顾春燕[1] 邵建国[1] 卞兆连[1] 王陆军[1] 

机构地区：[1]南通大学附属南通第三医院肝病中心,江苏南通226006 [2]南通大学公共卫生学院,江苏南通226019 [3]南通大学医学院,江苏南通226001

出　　处：《微生物学免疫学进展》2017年第3期7-13,共7页Progress In Microbiology and Immunology

基　　金：国家自然科学基金面上项目(81370520);江苏省自然科学基金面上项目(BK2012653)

摘　　要：目的通过实验性自身免疫性肝炎(experimental autoimmune hepatitis,EAH)小鼠模型,探讨γδT细胞及其分泌的细胞因子在EAH小鼠中的表达及意义。方法建立EAH小鼠模型,并予不同的干预措施,用ELISA检测小鼠肝脏组织中的IL-17水平,用流式细胞仪检测肝脏淋巴细胞亚群中IL-17的表达,根据肝脏病理组织学及血清中肝功能生化指标的变化,观察中和抗体对EAH小鼠肝脏损伤程度的影响。结果模型组小鼠肝脏IL-17表达较对照组显著升高且与炎症程度正相关(r=0.82,P<0.01),模型组肝脏淋巴亚群比例无明显变化,而γδT细胞中IL-17+比例显著高于对照组(P<0.01)。中和IL-17组小鼠的肝脏炎症明显轻于rat Ig G对照组(P<0.01),接近空白对照组(P>0.05);γδT细胞清除组小鼠的肝脏炎症明显轻于hamster Ig G对照组(P<0.05),但仍高于空白对照组(P<0.05)。结论 EAH小鼠中升高的IL-17主要来源于γδT细胞,中和IL-17或γδT细胞均可抑制或减轻炎症,提示肝脏γδT细胞通过IL-17参与EAH致病机制。Objective To investigate the roles of γδT cells and their cytokines in a mouse model with experimental autoimmune hepatitis（EAH）. Methods The EAH mouse model was established and several intervention procedures were applied. The level of interleukin-17 （ IL-17 ） was determined by ELISA in superuatant of liver homogenates. The intracellular IL-17 expression was analysed with flow cytometry in hepatic lymphocyte subsets. Serum biochemical markers and liver his- topathological features were detected to estimate the effects from blocking or neutralizaing antibodies on hepatic inflammation. Results The level of IL-17 in the supernatant of liver homogenates from the tested group was significantly increased in comparison with that in the control group, and positively correlated to the grades of hepatic inflammation （ r = 0.82 ,P 〈 0.01 ）. There were no obvious changes in precantages of cell subsets in mouse EAH group, only IL-17＋ hepatic γδT cells were significantly increased in comparison with the control group （ P 〈 0.01 ）. After neutralization of IL-17 with monoclonal antibody { mAb） , or depletion of γδT cells, the liver inflammation was significant relieved. Conclusion The increased IL-17 in mouse EAH model may be mainly secreted from γδT cells. Neutralization or blockade IL-17 or γδT cells, consequently, led to inhibit or relieve the inflammation, which indicated γδT cells playing an important role in the pathogenesis of EAH via IL-17 expression.

关 键 词：实验性自身免疫性肝炎 小鼠模型 白细胞介素-17 ΓΔT细胞 

分 类 号：R575.1[医药卫生—消化系统]