Th2与ILC2细胞在哮喘模型中的数量及产生细胞因子的比较研究  

Comparison of quantity and cytokine production of Th2 and ILC2 cells in murine models for asthma

作　　者：刁渔汉 李艳[1] 杨义然 陈茜文[1] 吕喆[1] 孙英[1] 王炜[1] DIAO Yu-han;LI Yan;YANG Yi-ran;CHEN Xi-wen;L Zhe;SUN Ying;WANG Wei(Department of Immunology,School of Basic Medical Sciences, Capital Medical University, Beijing 100069,China)

机构地区：[1]首都医科大学基础医学院免疫学系,北京100069

出　　处：《微生物学免疫学进展》2019年第1期26-35,共10页Progress In Microbiology and Immunology

基　　金：国家自然科学基金(81373177;81471594;81700026)

摘　　要：目的比较过敏原依赖和非依赖性哮喘模型中2型辅助性T细胞(Th2 cell)和固有淋巴样2型细胞(type 2innate lymphoid cell,ILC2)的功能。方法滴鼻法制备过敏原卵清蛋白(ovalbumin,OVA)和上皮源性细胞因子(IL-25、IL-33)诱导的亚急性和慢性哮喘小鼠模型。收集小鼠肺泡灌洗液(bronchoalvelar lavage fluid,BALF)进行细胞计数;取左肺进行石蜡包埋、切片和HE染色;右肺行流式细胞术,以分析在不同时间点各组小鼠Th2细胞和ILC2细胞数目和占肺组织总细胞比例,并对Th2型细胞因子的来源进行分析。结果与生理盐水组相比,各实验组BALF中总细胞数明显增加; HE染色可见OVA、IL-25和IL-33均可诱导哮喘典型病理学改变;各实验组肺组织中Th2细胞与ILC2细胞均明显上升,数量上以Th2细胞为主,两者均可产生Th2型细胞因子IL-5和IL-13,且以Th2细胞为主。而在致哮喘样改变、促进Th2细胞和ILC2细胞在小鼠肺部聚集等方面,以IL-33的效应最强。结论在过敏原OVA和非过敏原IL-25、IL-33诱导的哮喘模型中,Th2型细胞因子主要来源均为Th2细胞,提示Th2细胞在哮喘的发生、发展中起到主要作用。IL-33可能是过敏性和非过敏性哮喘患者个体化治疗的潜在靶点。Objective To compare the function of the Th2 and ILC2 cells in murine models for allergen-dependent and non-allergen-dependent asthma. Method Murine models for allergen-dependent and -independent asthma were developed by using intra-nasal instillation challenge with ovalbumin (OVA) and epithelial cytokines IL-25/IL-33, respectively. Histology examination was employed to analyze cell counting in bronchoalveolar lavage fluid (BALF) and pathological changes of lungs tissues. Flow cytometry was used in evaluation of ratio of the Th2 and ILC2 cells and distribution of Th2-type cytokines IL-5 and IL-13 in lungs tissues obtained from the mouse model. Results Compared with the control group (NS), the total numbers of cells in BALF were significantly increased in OVA-, IL-25 and IL-33-injected at both sub-acute (24 d) and chronic (36 d) phases ( p <0.05). At the day 36, the total numbers of cells in BALF from IL-25- and IL-33-injected mice were significantly higher than those of NS-injected mice ( p <0.05). There were the increased number of infiltration of inflammatory cells, mucosal folds, mucus production and the narrowed bronchia lumen of airways by histological staining in both OVA- and IL-25/IL-33-injected mice. Flow cytometry showed that the numbers of Th2 and ILC2 cells were significantly increased in lungs tissues of the tested groups compared with the control group. Th2 type cytokines IL-5 and IL-13 were produced by Th2 and ILC2 cells, and Th2 was a major producer.The IL-33 resulted in a predominant effect in pathogenesis in mouse model for asthma. Conclusion The Th2 cells are major source for Th2 type cytokines IL-5 and IL-13 in both allergen-dependent (OVA-induced) and -independent (IL-25/IL-33-induced) murine models for asthma. It suggests that Th2 cells play a important role in occurrence and development in asthma. IL-33 could be as a potential target in treatment of these two types of asthma.

关 键 词：哮喘 2型辅助性T细胞 固有淋巴样2型细胞 白介素-5 白介素-13 

分 类 号：R562.25[医药卫生—呼吸系统]