IL-25R+ circulating fibrocytes are increased in asthma and correlate with fixed airflow limitation
IL-25R+ circulating fibrocytes are increased in asthma and correlate with fixed airflow limitation
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DOI：
10.1111/crj.13433
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发表时间：
2021-08-12
影响因子：
1.7
通讯作者：
Zhang, Luo
中科院分区：
文献类型：
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作者：
Yao, Xiujuan;Liu, Xiaofang;Zhang, Luo
白细胞介素（IL）-25是一种辅助性T细胞（Th）2型细胞因子，与哮喘的发病机制有关。纤维细胞是可以迁移到循环和发炎的支气管上皮中的祖细胞。目的探讨循环纤维细胞可能是IL-25作用的新靶点，IL-25 R（+）循环纤维细胞的募集可能与哮喘气道阻塞相关。方法采用流式细胞术检测IL-25 R（+）成纤维细胞（即，对35例哮喘患者和15例正常对照者外周血单个核细胞（PBMC）中IL-17 RB（+）纤维细胞进行计数和比较。采用酶联免疫吸附法（ELISA）检测血浆IL-25水平。结果哮喘患者PBMC中总纤维细胞和IL-25 R（+）（IL-17 RB（+））纤维细胞的比例明显高于对照组。亚组分析进一步显示，在重度至极重度固定气流受限的哮喘患者中，PBMC中循环总纤维细胞和IL-25 R（+）纤维细胞的百分比显著增加。哮喘患者外周血中IL-25 R（+）水平与1秒用力呼气量/用力肺活量（FEV 1/FVC）、FEV1%预测值、血嗜酸性粒细胞、血清IgE和血浆IL-25水平显著相关。结论循环纤维细胞是IL-25的潜在靶细胞。哮喘患者IL-25 R（+）纤维细胞增加。IL-25 R（+）纤维细胞比例增加预示着固定气流受限的独特哮喘表型。以IL-25-纤维细胞轴为靶点的生物治疗可能为控制伴有严重气道重塑和阻塞的哮喘患者提供巨大的希望。
Introduction Interleukin (IL)-25 is a T helper (Th) type-2 cytokine implicated in the pathogenesis of asthma. Fibrocytes are progenitor cells that can migrate into circulation and inflamed bronchial epithelium. Objectives We aim to test the hypothesis that circulating fibrocytes may be the novel cellular targets of IL-25 and the recruitment of IL-25R(+) circulating fibrocytes may correlate with asthmatic airway obstruction. Methods By using flow cytometry analysis, IL-25R(+) fibrocytes (i.e., IL-17RB(+) fibrocytes) in the freshly isolated peripheral blood mononuclear cells (PBMCs) from 15 control subjects and 35 patients with asthma were enumerated and compared. Enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma levels of IL-25. Results We found the percentage of total and IL-25R(+) (IL-17RB(+)) fibrocytes in PBMCs was significantly increased in patients with asthma when compared with control subjects. Subgroup analysis further showed that the percentage of circulating total and IL-25R(+) fibrocytes in PBMCs was markedly increased in asthma patients with severe-to-very severe fixed airflow limitation. Furthermore, IL-25R(+) circulating fibrocytes in asthma patients were shown to significantly correlate with forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC), FEV1% predicted, blood eosinophils, serum IgE and plasma IL-25 levels. Conclusion We concluded that circulating fibrocytes are the novel potential cellular targets of IL-25. IL-25R(+) fibrocytes are increased in asthma patients. Increased proportions of IL-25R(+) fibrocytes predict a distinct asthma phenotype with fixed airflow limitation. Biological therapy-targeting IL-25-fibrocytes axis may offer great promise for the control of asthma patients with severe airway remodelling and obstruction.