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中国循证儿科杂志

中国循证儿科杂志 ›› 2018, Vol. 13 ›› Issue (3): 205-209.

• 论著 • 上一篇    下一篇

PM2.5促进Th9细胞分化及在哮喘发病中作用的初步研究

付劲蓉1,3,孙立成1,3,夏莉1,刘丽娟1,黄赛花1,韩晓1,周玉峰1,2   

  1. 1 复旦大学附属儿科医院和生物医学研究院上海，201102； 2 卫生部新生儿疾病重点实验室上海，201102；3 共同第一作者
  • 收稿日期:2018-06-20 修回日期:2018-06-25 出版日期:2018-06-24 发布日期:2018-06-25
  • 通讯作者: 周玉峰

Exposure to PM2.5 enhances Th9 cell differentiation and its role in the pathology of asthma

FU Jin-rong 1,3, SUN Li-cheng 1 ,3, XIA Li 1, LIU Li-juan 1, HUANG Sai-hua1 , HAN Xiao1 , ZHOU Yu-feng 1,2   

  1. 1 Children's Hospital and Institute of Biomedical Sciences of Fudan University, Shanghai 201102, China; 2 Key Laboratory of Neonatal Diseases, Ministry of Health, Shanghai 201102, China; 3 Co-first author
  • Received:2018-06-20 Revised:2018-06-25 Online:2018-06-24 Published:2018-06-25
  • Contact: ZHOU Yu-feng

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摘要： 目的：探讨PM2.5对Th9细胞分化的影响及其在哮喘发病中的作用，为揭示空气污染与哮喘发作的关系及发现新的防治策略提供实验证据。方法：采用蟑螂提取物（CRE）作为过敏原建立小鼠哮喘模型,在激发阶段向小鼠气道内滴加不同浓度的PM2.5悬液，通过肺泡灌洗液（BAL）细胞计数、肺部切片HE染色和气道阻力检测来判定PM2.5是否能加重哮喘的发生。流式细胞术检测肺门淋巴结中Th9细胞比例；荧光定量PCR（qPCR）检测肺组织匀浆中IL-9基因的表达。在体外分离CD4+幼稚T细胞，用TGF-β和IL-4诱导CD4+幼稚T细胞分化为Th9细胞，用流式细胞术、qPCR检测PM2.5对Th9细胞分化及对相关转录因子PU.1、B细胞活化转录因子（BATF）的影响。 结果：与单纯CRE激发的小鼠哮喘模型相比，PM2.5与CRE联合处理组（PM2.5+CRE）能显著增强哮喘炎症反应，PM2.5+CRE组小鼠的肺泡灌洗液中总细胞计数、嗜酸性粒细胞、中性粒细胞、巨噬细胞和淋巴细胞的数量较CRE组均明显上升，肺部被炎症细胞浸润的程度及气道阻力较CRE组明显增加。PM2.5+CRE能显著上调肺组织中IL-9表达以及肺门淋巴结中Th9阳性细胞比例。体外分化细胞中，PM2.5+CRE组IL-9阳性细胞的比例（52.0±5.8）%较CRE组（31.7±3.2）%明显增高(P=0.000 4)。PM2.5能显著上调IL-9及PU.1、BATF等Th9细胞调控基因的表达。结论：大气细颗粒物PM2.5可加重过敏原诱发的哮喘炎症，在体内外可显著增强Th9细胞的分化，提示PM2.5可能通过增强Th9细胞的分化加重哮喘。

Abstract: Objective：To explore the role of exposure to PM2.5 on Th9 cell differentiation and its role in the pathology of asthma to provide evidence for causal relationship between air pollution and asthma and to find new treatment strategy for asthma. Methods：Mice were sensitized and challenged with cockroach extract (CRE) by intratracheal inhalation. Different dose of PM2.5 were inhaled by intratracheal injection during the challenging period. Cell counting in the bronchoalveolar lavage fluid (BALF), HE staining of lung tissues and resistance of airway were detected to evaluate the effect of PM2.5 on asthma. Th9 cells in the lung hilar lymphnodes was detected with flow cytometry. IL-9 expression in the lung tissues was detected with qRT-PCR. Th9 cells were differentiated in the presence of IL-4 and TGF-β with naive CD4+ T cells in vitro. IL-9，PU.1 and BATF were detected with qRT-PCR or flow cytometry. Results：The lung inflammation were significant enhanced in the PM2.5 together with allergen (CRE) group compared with CRE group. The total cell numbers, the number of eosinophils, granulocytes and lymphocytes in the BALF, lung inflammation, and airway resistance were significant increased in the PM2.5+CRE group compared with CRE group. There was more Th9 positive cells in lung hilar lymphonodes in the PM2.5+CRE group than CRE group. The IL-9 positive cells was more in the PM2.5+CRE group than CRE group in in-vitro experiment (52.0%±5.8% vs 31.7%±3.2%, P=0.000 4 ). PU.1 and BATF expression was also higher in the PM2.5+CRE group than CRE group. Conclusion：PM2.5 could enhance the inflammation of asthma and this may be related to its effect on Th9 cells differentiation.