Essential role of IL-23 in the development of acute exacerbation of pulmonary fibrosis
Essential role of IL-23 in the development of acute exacerbation of pulmonary fibrosis
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DOI：
10.1152/ajplung.00582.2020
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发表时间：
2021-11-01
影响因子：
4.9
通讯作者：
Miyahara, Nobuaki
中科院分区：
文献类型：
--
作者：
Senoo, Satoru;Taniguchi, Akihiko;Miyahara, Nobuaki
特发性肺纤维化急性加重预后不良，与中性粒细胞炎症相关。 Interleukin-23 是一种参与中性粒细胞炎症的促炎细胞因子。然而，对其在肺纤维化急性加重中的作用知之甚少。本研究旨在确定白细胞介素 23 在肺纤维化急性加重中的作用。为了评估肺纤维化的急性恶化，给小鼠气管内施用博莱霉素，然后施用脂多糖。分析了肺部的炎症细胞、细胞因子水平和形态学形态测量。测量有或没有急性加重的特发性肺纤维化患者的支气管肺泡灌洗液中的细胞因子水平。肺纤维化急性加重的小鼠气道中白细胞介素 23、-17A 和 -22 水平升高。与野生型小鼠相比，患有肺纤维化急性加重的白细胞介素 23p19 缺陷小鼠，与白细胞介素 17A 和 -22 水平降低相关的气道炎症和纤维化明显减轻。使用抗白细胞介素 23 抗体治疗可减轻肺纤维化急性恶化小鼠的气道炎症和纤维化，并降低白细胞介素 17A 和 -22 水平。 17 型辅助 T 细胞是肺纤维化急性加重小鼠中白细胞介素 17A 的主要来源。特发性肺纤维化患者的支气管肺泡灌洗液中白细胞介素 23 水平往往高于未急性加重的特发性肺纤维化患者。这里提供的数据表明，白细胞介素23对于肺纤维化急性加重的发展至关重要，并且阻断白细胞介素23可能是肺纤维化急性加重的新治疗策略。
Acute exacerbation of idiopathic pulmonary fibrosis has a poor prognosis associated with neutrophilic inflammation. Interleukin-23 is a proinflammatory cytokine involved in neutrophilic inflammation. However, little is known about its role in acute exacerbation of pulmonary fibrosis. This study was performed to determine the role of interleukin-23 in acute exacerbation of pulmonary fibrosis. For assessment of acute exacerbation of pulmonary fibrosis, mice were intratracheally administered bleomycin followed by lipopolysaccharide. Inflammatory cells, cytokine levels, and morphological morphometry of the lungs were analyzed. Cytokine levels were measured in the bronchoalveolar lavage fluid of idiopathic pulmonary fibrosis patients with or without acute exacerbation. Interleukin-23, -17A, and -22 levels were increased in the airway of mice with acute exacerbation of pulmonary fibrosis. Interleukin-23p19-deficient mice with acute exacerbation of pulmonary fibrosis had markedly reduced airway inflammation and fibrosis associated with decreased levels of interleukin-17A and -22 compared with wild-type mice. Treatment with an anti-interleukin-23 antibody attenuated airway inflammation and fibrosis and reduced interleukin-17A and -22 levels in mice with acute exacerbation of pulmonary fibrosis. T-helper type 17 cells were the predominant source of interleukin-17A in mice with acute exacerbation of pulmonary fibrosis. Interleukin-23 levels in bronchoalveolar lavage fluid tended to be higher in idiopathic pulmonary fibrosis patients with than without acute exacerbation. The data presented here suggest that interleukin-23 is essential for the development of acute exacerbation of pulmonary fibrosis and that blockade of interleukin-23 may be a new therapeutic strategy for acute exacerbation of pulmonary fibrosis.