T helper type 17-related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients
T helper type 17-related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients
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DOI：
10.1111/j.1365-2249.2009.03965.x
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发表时间：
2009-08-01
影响因子：
4.6
通讯作者：
Balbi, B.
中科院分区：
文献类型：
--
作者：
Di Stefano, A.;Caramori, G.;Balbi, B.
缓解期慢性阻塞性肺疾病(COPD)患者支气管粘膜中活化的T淋巴细胞数量增多。辅助型T细胞(Th17)在IL-22和IL-23的调控下，释放IL-17作为其效应细胞因子。此外，在某些慢性炎症性疾病中，Th17细胞数量增加。目的探讨IL-17A、IL-17F、IL-21、IL-22、IL-23及Th17细胞标志维甲酸孤儿受体RORC2在不同病情的稳定期慢性阻塞性肺疾病(COPD)患者肺组织中的表达，并与年龄匹配的对照组进行比较。免疫组织化学和/或定量聚合酶链式反应检测IL-17A、IL-17F、IL-21、IL-22、IL-23和RORC2在支气管黏膜中的表达。缓解期COPD患者支气管上皮中IL-22(+)和IL-23(+)免疫反应细胞数较对照组明显增多。此外，稳定期COPD患者支气管黏膜下层IL-17A(+)和IL-22(+)免疫反应细胞数较对照组非吸烟者增多。在所有吸烟者、有无疾病和单独患有COPD的患者中，IL-22(+)细胞的数量与支气管粘膜中的CD4(+)和CD8(+)细胞的数量显著相关。肺功能正常吸烟者与COPD吸烟者支气管黏膜RORC2基因表达差异无统计学意义。此外，我们报告内皮细胞表达高水平的IL-17A和IL-22。与Th17相关的细胞因子IL-17A、IL-22和IL-23在COPD患者中的表达增加可能反映了他们以及特定的IL-17产生细胞参与了COPD的慢性炎症。
There are increased numbers of activated T lymphocytes in the bronchial mucosa of stable chronic obstructive pulmonary disease (COPD) patients. T helper type 17 (Th17) cells release interleukin (IL)-17 as their effector cytokine under the control of IL-22 and IL-23. Furthermore, Th17 numbers are increased in some chronic inflammatory conditions. To investigate the expression of interleukin (IL)-17A, IL-17F, IL-21, IL-22 and IL- 23 and of retinoic orphan receptor RORC2, a marker of Th17 cells, in bronchial biopsies from patients with stable COPD of different severity compared with age-matched control subjects. The expression of IL-17A, IL-17F, IL-21, IL- 22, IL-23 and RORC2 was measured in the bronchial mucosa using immunohistochemistry and/or quantitative polymerase chain reaction. The number of IL-22(+) and IL-23(+) immunoreactive cells is increased in the bronchial epithelium of stable COPD compared with control groups. In addition, the number of IL-17A(+) and IL-22(+) immunoreactive cells is increased in the bronchial submucosa of stable COPD compared with control non-smokers. In all smokers, with and without disease, and in patients with COPD alone, the number of IL-22(+) cells correlated significantly with the number of both CD4(+) and CD8(+) cells in the bronchial mucosa. RORC2 mRNA expression in the bronchial mucosa was not significantly different between smokers with normal lung function and COPD. Further, we report that endothelial cells express high levels of IL-17A and IL-22. Increased expression of the Th17-related cytokines IL-17A, IL-22 and IL-23 in COPD patients may reflect their involvement, and that of specific IL-17-producing cells, in driving the chronic inflammation seen in COPD.