Th17转录因子RORγt和BATF及Th17相关细胞因子在中性粒细胞亚型哮喘发病中的作用

doi:10.13481/j.1671-587x.20170121

吉林大学学报(医学版) ›› 2017, Vol. 43 ›› Issue (01): 106-110.doi: 10.13481/j.1671-587x.20170121

Th17转录因子RORγt和BATF及Th17相关细胞因子在中性粒细胞亚型哮喘发病中的作用

王国强¹, 王昱博¹, 张维杰², 王歆然¹, 张文锦¹, 吴恬¹, 关雪娃¹, 陈芳¹, 郑敬彤¹, 王放¹

1. 吉林大学基础医学院病原生物学教研室, 吉林长春 130021;
2. 吉林省人民医院呼吸科, 吉林长春 130021

收稿日期:2016-06-16 出版日期:2017-01-28 发布日期:2017-02-08
通讯作者: 王放,教授,博士研究生导师(Tel:0431-85619574,E-mail:wf@jlu.edu.cn) E-mail:wf@jlu.edu.cn
作者简介:王国强(1991-),男,山西省晋中市人,在读医学硕士,主要从事病原生物学和呼吸道疾病发病机制方面的研究。
基金资助:
吉林省科技厅科技发展计划-科技创新人才培育计划资助课题（20150519015JH）；吉林大学大学生创新创业训练计划国家级项目资助课题（2015791156）；吉林大学白求恩B计划资助课题（2012218）

Effects of Th17 transcription factors RORγt, BATF and Th17-related cytokines in pathogenesis of patients with neutrophilic asthma

WANG Guoqiang¹, WANG Yubo¹, ZHANG Weijie², WANG Xinran¹, ZHANG Wenjin¹, WU Tian¹, GUAN Xuewa¹, CHEN Fang¹, ZHENG Jingtong¹, WANG Fang¹

1. Department of Pathogen Biology, School of Basic Medical Sciences, Jilin University, Changchun 130021, China;
2. Department of Respiratory Medicine, People's Hospital, Jilin Province, Changchun 130021, China

Received:2016-06-16 Online:2017-01-28 Published:2017-02-08

摘要/Abstract

摘要：

目的：检测中性粒细胞亚型哮喘（NA）患者痰上清中辅助性T细胞17（Th17）特异性转录因子维甲酸相关核孤儿受体γt（RORγt）、B细胞转录激活因子（BATF）及外周血中Th17细胞相关细胞因子白细胞介素8（IL-8）、白细胞介素17（IL-17）和白细胞介素22（IL-22）表达水平，探讨其在NA发病中的作用。方法：以56例支气管哮喘患者为研究对象，4.5%生理盐水雾化诱导痰，经细胞MGG染色进行哮喘的炎症亚型分型，分为嗜酸性粒细胞亚型哮喘（EA）组（26例）和NA组（30例），以常规体检者为健康对照组（NC组，28人）。实时荧光定量PCR（RT-PCR）法检测痰上清中BATF和RORγt mRNA表达水平。空腹抽取各组研究对象肘静脉血10 mL，Ficoll密度梯度离心后分离外周血单个核细胞（PBMC），ELISA法测定血清中IL-8、IL-17和IL-22蛋白表达水平，流式细胞术检测PBMC中Th17细胞（CD4⁺IL-17⁺细胞）的百分率。结果：与NC组和EA组比较，NA组患者血清中IL-8、IL-17和IL-22表达水平均明显升高（P<0.05）；与NC组比较，EA组患者血清中IL-8、IL-17和IL-22表达水平差异无统计学意义（P>0.05）。与NC组和EA组比较，NA组患者痰上清中BATF和RORγt mRNA表达水平明显升高（P<0.01）。与NC组和EA组比较，NA组患者PBMC中Th17细胞百分率均明显升高（P<0.01）；与NC组比较，EA组患者PBMC中Th17细胞百分率差异无统计学意义（P>0.05）。结论：IL-17转录因子RORγt和BATF参与了NA患者气道炎症发生过程，且Th17细胞及其相关细胞因子IL-17和IL-22的异常表达与NA的全身反应有关联。

关键词: 中性粒细胞亚型哮喘, B细胞转录激活因子, 维甲酸相关核孤儿受体γt, 辅助性T细胞17

Abstract:

Objective: To detect the expression levels of retinoic acid-related orphan receptor γt (RORγt),B cell activating transcription factor(BATF) in sputum of the patients with neutrophilic asthma(NA),Th17 cells-related cytokines such as interleukin-8(IL-8),IL-17, and IL-22 in peripheral blood,and to investigate their effects in the pathogenesis of NA.Methods: Fifty-six patients with asthma were selected as subjects and the sputum was induced with 45% normal saline.According to the results of sputum smear by MGG staining,they were divided into eosinophilic asthma group (EA,n=26) and NA group (n=30).28 cases of healthy volunteers were selected as control group. The expression levels of IL-8,IL-17, and IL-22 in serum were detected by ELISA and the expressions of BATF and RORγt mRNA in sputum were determined by RT-PCR. And T-lymphocytes were collected from the peripheral blood mononuclear cells (PBMC),and then the percentages of Th17 cells were determined by flow cytometry.Results: Compared with NC and EA groups,the levels of IL-8,IL-17, and IL-22 in serum of the patients in NA group were significantly increased (P<0.05),but there were no significant differences between EA and NC groups(P>0.05).Compared with NC and EA groups,the expression levels of BATF and RORγt mRNA were significantly increased (P<0.01); compared with NC and EA groups, the percentage of Th17 cells in PBMC of the pathents in NA group was significantly increased (P<0.01),but there was no significant difference between EA and NC groups(P>0.05).Conclusion: RORγt and BATF involve in the onset and development of airway inflammation in the patients with NA,and Th17 cells as well as Th17-related cytokines such as IL-17 and IL-22 may be closely associated with systematic resposes of NA.

Key words: neutrophilic asthma, T helper cells 17, retinoic acid-related orphan receptor γt, B cell activating transcription factor

中图分类号:

R562.25

王国强, 王昱博, 张维杰, 王歆然, 张文锦, 吴恬, 关雪娃, 陈芳, 郑敬彤, 王放. Th17转录因子RORγt和BATF及Th17相关细胞因子在中性粒细胞亚型哮喘发病中的作用[J]. 吉林大学学报(医学版), 2017, 43(01): 106-110.

WANG Guoqiang, WANG Yubo, ZHANG Weijie, WANG Xinran, ZHANG Wenjin, WU Tian, GUAN Xuewa, CHEN Fang, ZHENG Jingtong, WANG Fang. Effects of Th17 transcription factors RORγt, BATF and Th17-related cytokines in pathogenesis of patients with neutrophilic asthma[J]. Journal of Jilin University Medicine Edition, 2017, 43(01): 106-110.

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Th17转录因子RORγt和BATF及Th17相关细胞因子在中性粒细胞亚型哮喘发病中的作用

Effects of Th17 transcription factors RORγt, BATF and Th17-related cytokines in pathogenesis of patients with neutrophilic asthma

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