Adult non-cystic fibrosis bronchiectasis is characterised by airway luminal Th17 pathway activation.

Adult non-cystic fibrosis bronchiectasis is characterised by airway luminal Th17 pathway activation.
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DOI:
10.1371/journal.pone.0119325
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Serisier DJ
Serisier DJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chen AC;Martin ML;Lourie R;Rogers GB;Burr LD;Hasnain SZ;Bowler SD;McGuckin MA;Serisier DJ

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非囊性纤维化(CF)支气管扩张症的特征是慢性气道感染和嗜酸性炎症,我们假设这与Th 17通路激活有关。对41例稳定期支气管扩张症患者和20例健康对照者的支气管肺泡灌洗液(BALF)中Th 17通路细胞因子进行定量,并对支气管内活检(EBx)中IL-17 A、IL-1β、IL-8和IL-23的基因表达进行测定。确定了IL-17 A水平与感染状态、重要临床指标和随后铜绿假单胞菌感染的关系。所有Th 17细胞因子的BALF水平(中位数(IQR)pg/mL)显著高于对照组,包括IL-17 A(1.73(1.19,3.23)vs. 0.27(0.24,0.35),95%CI 1.05至2.21,p<0.0001)和IL-23(9.48(4.79,15.75)vs. 0.70(0.43,1.79),95%CI 4.68至11.21,p<0.0001)。然而,BALF IL-17 A水平与临床指标或气道微生物学无关,也不能预测随后的铜绿假单胞菌感染。此外,支气管扩张EBx中IL-17 A的基因表达与对照组无差异。相反,基因表达支气管扩张症EBx组IL 1 β(相对于对照组中位数)显著高于对照组(4.12(1.24,8.05)vs 1(0.13,2.95),95% CI 0.05至4.07,p = 0.04)和IL-8(3.75(1.64,11.27)vs 1(0.54,3.89),95% CI 0.32至4.87,p = 0.02)和BALF IL-8和IL-1α水平显示与临床指标和气道微生物学显著相关。铜绿假单胞菌感染与IL-8水平升高相关,而流感嗜血杆菌感染与IL-1α水平升高相关。确定的成人非CF支气管扩张的特征在于管腔Th 17途径活化,然而,该途径可能相对不如非抗原特异性先天性嗜酸性免疫的活化重要。
Non-cystic fibrosis (CF) bronchiectasis is characterised by chronic airway infection and neutrophilic inflammation, which we hypothesised would be associated with Th17 pathway activation. Th17 pathway cytokines were quantified in bronchoalveolar lavage fluid (BALF), and gene expression of IL-17A, IL-1β, IL-8 and IL-23 determined from endobronchial biopsies (EBx) in 41 stable bronchiectasis subjects and 20 healthy controls. Relationships between IL-17A levels and infection status, important clinical measures and subsequent Pseudomonas aeruginosa infection were determined. BALF levels of all Th17 cytokines (median (IQR) pg/mL) were significantly higher in bronchiectasis than control subjects, including IL-17A (1.73 (1.19, 3.23) vs. 0.27 (0.24, 0.35), 95% CI 1.05 to 2.21, p<0.0001) and IL-23 (9.48 (4.79, 15.75) vs. 0.70 (0.43, 1.79), 95% CI 4.68 to 11.21, p<0.0001). However, BALF IL-17A levels were not associated with clinical measures or airway microbiology, nor predictive of subsequent P. aeruginosa infection. Furthermore, gene expression of IL-17A in bronchiectasis EBx did not differ from control. In contrast, gene expression (relative to medians of controls) in bronchiectasis EBx was significantly higher than control for IL1β (4.12 (1.24, 8.05) vs 1 (0.13, 2.95), 95% CI 0.05 to 4.07, p = 0.04) and IL-8 (3.75 (1.64, 11.27) vs 1 (0.54, 3.89), 95% CI 0.32 to 4.87, p = 0.02) and BALF IL-8 and IL-1α levels showed significant relationships with clinical measures and airway microbiology. P. aeruginosa infection was associated with increased levels of IL-8 while Haemophilus influenzae was associated with increased IL-1α. Established adult non-CF bronchiectasis is characterised by luminal Th17 pathway activation, however this pathway may be relatively less important than activation of non-antigen-specific innate neutrophilic immunity.
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