mTSLPR-Ig调节CD11c^+细胞改善哮喘小鼠炎症反应  

Fusion protein mTSLPR-Ig regulates CD11c^+ cells and improve the inflammatory reactions in a mouse model of asthma

作　　者：张方[1] 施毅[1] 李子玲[1] 胡波[2] 宋勇[1] 

机构地区：[1]南京军区南京总医院呼吸内科 [2]南京军区联勤部卫生部,南京210002

出　　处：《现代免疫学》2011年第1期33-37,共5页Current Immunology

基　　金：中国博士后科学基金资助项目(20070411050);江苏省博士后科研资助计划项目(0701023B)

摘　　要：本研究探讨mTSLPR-Ig逆转哮喘小鼠Th1/Th2失衡以及改善哮喘气道炎症的可行性及其诱导哮喘免疫耐受的机制。实验包括用卵白蛋白(OVA)腹腔注射致敏和雾化吸入激发BALB/c小鼠,建立哮喘动物模型。于OVA激发前,将mTSLPR-Ig进行小鼠滴鼻灌注,光镜下对BALF中细胞总数及嗜酸粒细胞、淋巴细胞进行计数;ELISA法检测BALF中细胞因子IL-4、IL-5、IFN-γ以及IL-10水平;HE组织染色法观察小鼠肺部炎症表现。分离小鼠肺脏并制备成细胞悬液,FCM检测肺脏CD11c+细胞表面共刺激分子CD80、CD86以及CD40的表达变化。结果表明,mTSLPR-Ig治疗组与哮喘组比较,BALF中细胞总数和嗜酸粒细胞计数显著减少(P<0.01)、BALF中IL-4、IL-5水平均显著降低(P<0.01),而IL-10、IFN-γ显著升高(P<0.01);小鼠肺部炎症明显减轻。mTSLPR-Ig治疗组肺脏CD11 c+细胞表面分子CD80、CD86以及CD40较哮喘组显著降低。mTSLPR-Ig能显著抑制哮喘小鼠Th1/Th2失衡以及肺部变应性炎症,该效应可能与mTSLPR-Ig抑制肺脏CD11 c+细胞共刺激分子表达有关。mTSLPR-Ig对哮喘的治疗具有重要的潜在临床应用价值,为哮喘的治疗提供了可能的新途径。Thymic stromal lymphopoietin（TSLP） activates CD11c＋ through the combination with its receptor （TSLPR） on the surface of CD11c＋ , thus resulting in Thl/Th2 imbalance in asthma. To study the feasibility of fusion protein mTSLPR-Ig constituted by the extracellular segment of mouse TSLPR and mouse Fc of Ig, to reverse Th1/Th2 imbalance and to improve airway inflammation in asthma mouse in order to explore the mechanism of mTSLPR-Ig inducing immune tolerance in asthma by regulating CD11c＋ , ovalbumin （OVA） was injected intraperitoneally and challenged with aerosol inhalation in BALB/c mice to establish an animal models of asthma. Before the OVA challenging, mTSLPR-Ig were infused intranasally in mice. The total number of cells in BALF, eosinophils and lymphocytes were counted with light microscope, and the levels of cytokines IL-4, IL-5, IFN-γ and IL-10 in BALF were evaluated with ELISA assay. The inflammatory reactions of lung was observed with HE staining. After the preparation of lungs tissues into cell suspension, the expression of co-stimulatory molecules CD80, CD86 and CD40 on the surface of CD11c＋ were detected with FCM assay. It was demonstrated that the airway inflammation, the counts of total cell and eosinophil, and IL-4, IL-5 level in BALF were significantly reduced in mTSLPR-Ig treated mice, while IL-10, IFN-γ level were enhanced. TSLPR-mIg treatment resulted in the reduction of CD80, CD86 and CD40 expression significantly. From these observation, it is evident that mTSLPR-Ig can inhibit allergic lung inflammation and Thl/ Th2 imbalance, which may be related to the expression suppression of the co-stimulatory molecules on pulmonary CD11c＋ by fusion protein mTSLPR-Ig, indicating that this fusion protein may have potential clinical value for the treatment of asthma, and providing a new way to treat this allergic disease.

关 键 词：哮喘 免疫耐受 CD11c^+细胞 TSLPR 可溶性受体 

分 类 号：R392.12[医药卫生—免疫学]