Department of Microbiology and Immunology, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Department of Pediatrics, Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Allergy. 2019 Apr;74(4):685-697. doi: 10.1111/all.13661. Epub 2018 Dec 4.
Chitinase 3-like 1 protein (CHI3L1) (YKL-40 in humans and breast regression protein [BRP]-39 in mice) is required for optimal allergen sensitization and Th2 inflammation in various chronic inflammatory diseases including asthma. However, the role of CHI3L1 in airway inflammation induced by respiratory viruses has not been investigated. The aim of this study was to investigate the relationship between CHI3L1 and airway inflammation caused by respiratory syncytial virus (RSV) infection.
We measured YKL-40 levels in human nasopharyngeal aspirate (NPA) from hospitalized children presenting with acute respiratory symptoms. Wild-type (WT) and BRP-39 knockout (KO) C57BL/6 mice were inoculated with live RSV (A2 strain). Bronchoalveolar lavage fluid and lung tissue samples were obtained on day 7 after inoculation to assess lung inflammation, airway reactivity, and expression of cytokines and BRP-39.
In human subjects, YKL-40 and IL-13 levels in NPA were higher in children with RSV infection than in control subjects. Expression of BRP-39 and Th2 cytokines, IL-13 in particular, was increased following RSV infection in mice. Airway inflammation caused by RSV infection was reduced in BRP-39 KO mice as compared to WT mice. Th2 cytokine levels were not increased in the lungs of RSV-infected BRP-39 KO mice. BRP-39 regulated M2 macrophage activation in RSV-infected mice. Additionally, treatment with anti-CHI3L1 antibody attenuated airway inflammation and Th2 cytokine production in RSV-infected WT mice.
These findings suggest that CHI3L1 could contribute to airway inflammation induced by RSV infection. CHI3L1 could be a potential therapeutic candidate for attenuating Th2-associated immunopathology during RSV infection.
几丁质酶 3 样蛋白 1 （CHI3L1）（人类的 YKL-40 和小鼠的乳腺回归蛋白 [BRP]-39）是各种慢性炎症性疾病（包括哮喘）中变应原致敏和 Th2 炎症所必需的。然而，CHI3L1 在呼吸道病毒引起的气道炎症中的作用尚未被研究。本研究旨在探讨 CHI3L1 与呼吸道合胞病毒（RSV）感染引起的气道炎症之间的关系。
我们测量了因急性呼吸道症状住院的儿童鼻咽抽吸物（NPA）中的 YKL-40 水平。野生型（WT）和 BRP-39 敲除（KO）C57BL/6 小鼠用活 RSV（A2 株）接种。接种后第 7 天，获取支气管肺泡灌洗液和肺组织样本，以评估肺炎症、气道反应性以及细胞因子和 BRP-39 的表达。
在人类受试者中，NPA 中的 YKL-40 和 IL-13 水平在 RSV 感染患儿中高于对照组。RSV 感染后，小鼠的 BRP-39 和 Th2 细胞因子，特别是 IL-13 的表达增加。与 WT 小鼠相比，BRP-39 KO 小鼠 RSV 感染引起的气道炎症减少。RSV 感染的 BRP-39 KO 小鼠肺中的 Th2 细胞因子水平未增加。BRP-39 调节 RSV 感染小鼠的 M2 巨噬细胞激活。此外，用抗-CHI3L1 抗体治疗可减轻 RSV 感染 WT 小鼠的气道炎症和 Th2 细胞因子产生。
这些发现表明 CHI3L1 可能有助于 RSV 感染引起的气道炎症。CHI3L1 可能是 RSV 感染期间减轻 Th2 相关免疫病理学的潜在治疗靶点。
