IL-33诱导的小鼠过敏原非依赖性哮喘样模型肺组织免疫细胞及亚群的改变

doi:10.3969/j.issn.1006-7795.2016.05.001

首都医科大学学报 ›› 2016, Vol. 37 ›› Issue (5): 561-567.doi: 10.3969/j.issn.1006-7795.2016.05.001

IL-33诱导的小鼠过敏原非依赖性哮喘样模型肺组织免疫细胞及亚群的改变

袁琳洁¹, 陈诗皓¹, 安高¹, 黄琼¹, 易达委¹, 李艳¹, 吕喆¹, 王晶晶², 黄克武³, 王炜¹, 孙英¹

1. 首都医科大学基础医学院免疫学系, 北京 100069;
2. 首都医科大学实验动物部, 北京 100069;
3. 首都医科大学附属北京朝阳医院呼吸与危重症医学科北京呼吸疾病研究所, 北京 100020

收稿日期:2016-06-30 出版日期:2016-10-21 发布日期:2016-10-19
通讯作者: 孙英 E-mail:ying.sun@ccmu.edu.cn
基金资助:
国家自然科学基金（81373177，81471594），北京市教育委员会科技发展计划面上项目（KM201410025006）0

Changes of immune cells and their subsets in lungs of interleukin (IL)-33-induced allergen-independent murine model of asthma

Yuan Linjie¹, Chen Shihao¹, An Gao¹, Huang Qiong¹, Yi Dawei¹, Li Yan¹, Lyu Zhe¹, Wang Jingjing², Huang Kewu³, Wang Wei¹, Sun Ying¹

1. Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China;
2. Department of Laboratory Animal Sciences, Capital Medical University, Beijing 100069, China;
3. Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing Institute of Respiratory Medicine, Beijing 100020, China

Received:2016-06-30 Online:2016-10-21 Published:2016-10-19
Supported by:
This study was supported by National Natural Science Foundation of China(81373177, 81471594),Science and Technology Project of the Beijing Municipal Education Commission (KM201410025006).

摘要/Abstract

摘要： 目的本研究旨在通过对白细胞介素-33（interleukin-33，IL-33）诱导的过敏原非依赖性哮喘样模型小鼠的观察，探索IL-33对小鼠肺组织中T、B淋巴细胞亚群，自然杀伤T（natural killer T，NKT）细胞和固有淋巴样2型细胞（type 2 innate lymphoid cells，ILC2）的生物学作用。方法采用数字表法将小鼠随机分为氯化钠注射液（normal saline，NS）组和IL-33组，分别将NS、IL-33于1~6 d连续滴鼻，之后隔天滴鼻至18 d制备小鼠哮喘模型。采用有创肺功能检测小鼠气道高反应性；肺组织切片染色观察气道炎性反应；流式细胞术检测小鼠肺组织中T、B细胞亚群，NKT细胞和ILC2细胞数量及比例变化。结果与NS组相比，鼻腔给予IL-33刺激可引起小鼠气道反应性增高，气道周围炎性细胞浸润和杯状细胞增生。IL-33组小鼠肺组织T细胞（CD3⁺T）及其亚群细胞数增多，Th2细胞（CD3⁺CD8^-IL-4⁺）出现优势分化，Th1/Th2细胞比例下降（P<0.01）；B细胞（CD19⁺B）及其亚群（B1a：CD19⁺CD23^-CD5⁺CD11b⁺，B1b：CD19⁺CD23^-CD5^-CD11b⁺和B2：CD19⁺CD23⁺B220⁺）以及ILC2细胞（lineage^-ICOS⁺ST2⁺）数出现明显增加（P<0.01）；NKT细胞（CD3⁺CD8^-CD49b⁺）比例无明显改变（P>0.05）。结论 IL-33可能通过直接或间接作用造成肺组织T、B淋巴细胞亚群和ILC2细胞的数量及比例改变，打破局部免疫系统平衡，引发哮喘炎性反应。

关键词: 白细胞介素-33, 哮喘, T淋巴细胞, B淋巴细胞, 固有淋巴样2型细胞

Abstract: Objective To explore effects of IL-33 on subsets of T cells and B cells, type 2 innate lymphoid cells (ILC2) and natural killer T (NKT) cells in lungs in IL-33-induced murine model of asthma.Methods Mice were randomly distributed into two groups including normal saline(NS, control group) and IL-33-challenged groups. Nasal challenges with recombinant mouse IL-33 or saline were daily performed from the day 1-6,followed by every 2 days for a further 12 days. Lung functions and histological staining of lung tissue sections were used to measure airways hyperresponsiveness and inflammation.Flow cytometry was employed to determine the changes of total and phenotypes of subsets of pulmonary T cells and B cells,NKT cells and ILC2 cells, compared with those of lung. Results Compared with the NS group intranasal challenge with IL-33 induced airways hyperresponsiveness, infiltrating inflammatory cells and goblet cell hyperplasia. IL-33-challenge also increased total pulmonary numbers of cells, total CD3⁺T cells and type 2 helper cells (CD3⁺CD8^-IL-4⁺) which leading to decrease of Th1/Th2 ratio (P<0.01). In addition, nasal challenge with IL-33 increased total number of CD19⁺B cells and their subsets (B1a:CD19⁺CD23^-CD5⁺CD11b⁺, B1b:CD19⁺CD23^-CD5^-CD11b⁺ and B2 B cells:CD19⁺CD23⁺B220⁺) as well as ILC2(lineage-ICOS⁺ST2⁺) (P<0.01), but not NKT cells (CD3⁺CD8^-CD49b⁺) (P>0.05).Conclusion Local challenge with IL-33 may play role in the pathogenesis of asthma through acting directly and/or indirectly on T cells, B cells and ILC2 cells, breaking the balance of immune system and causing immune dysfunction.

Key words: interleukin-33, asthma, T lymphocytes, B lymphocytes, type 2 innate lymphoid cells

中图分类号:

R392

袁琳洁, 陈诗皓, 安高, 黄琼, 易达委, 李艳, 吕喆, 王晶晶, 黄克武, 王炜, 孙英. IL-33诱导的小鼠过敏原非依赖性哮喘样模型肺组织免疫细胞及亚群的改变[J]. 首都医科大学学报, 2016, 37(5): 561-567.

Yuan Linjie, Chen Shihao, An Gao, Huang Qiong, Yi Dawei, Li Yan, Lyu Zhe, Wang Jingjing, Huang Kewu, Wang Wei, Sun Ying. Changes of immune cells and their subsets in lungs of interleukin (IL)-33-induced allergen-independent murine model of asthma[J]. Journal of Capital Medical University, 2016, 37(5): 561-567.

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IL-33诱导的小鼠过敏原非依赖性哮喘样模型肺组织免疫细胞及亚群的改变

Changes of immune cells and their subsets in lungs of interleukin (IL)-33-induced allergen-independent murine model of asthma

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