Chitinase 3‐like 1 protein plays a critical role in respiratory syncytial virus‐induced airway inflammation

• Published in: Allergy (Copenhagen) Vol. 74; no. 4; pp. 685 - 697
• Main Authors: Kim, Min Jung, Shim, Doo Hee, Cha, Hye‐Ran, Moon, Kuk‐Young, Yang, Chang Mo, Hwang, Su Jin, Kim, Kyung Won, Park, Jeon Han, Lee, Chun Geun, Elias, Jack A., Sohn, Myung Hyun, Lee, Jae Myun
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.04.2019; John Wiley and Sons Inc
• Subjects: Allergens; Alveoli; Animals; Asthma; Asthma - virology; bronchiolitis; Bronchus; Case-Control Studies; Cell activation; Child; Children; Chitinase; chitinase 3‐like 1 protein; Chitinase-3-Like Protein 1 - adverse effects; Chitinase-3-Like Protein 1 - analysis; Cytokines; Cytokines - metabolism; Female; Growth Substances; Humans; Infections; Inflammation; Inflammation - virology; Inflammatory diseases; Inoculation; lower respiratory tract infection; Lungs; Lymphocytes T; Macrophages; Measurement methods; Mice; Mice, Inbred C57BL; Original; ORIGINAL ARTICLES; Proteins; Respiratory syncytial virus; Respiratory Syncytial Virus Infections - complications; Respiratory Syncytial Viruses; Respiratory System - pathology; Respiratory System - virology; Respiratory tract; Respiratory tract diseases; Rodents; type 2 immunity; respiratory syncytial viruses; chitinase 3-like 1 protein; type 2 immunity; bronchiolitis; lower respiratory tract infection
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/all.13661

Background 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. Methods 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. Results 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. Conclusion 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. Respiratory syncytial virus infection induces increased expression of BRP‐39 by macrophages and epithelial cells that is related to Th2 inflammation. A lack of BRP‐39 attenuates RSV‐induced airway inflammation and IL‐13 responses. BRP‐39 is an important regulator of RSV infection and suggested as a potential therapeutic target for RSV‐related respiratory illness.