The potential roles and mechanisms of Chitinase-3-like-1 in the pathogenesis of type 2-biased airway diseases.

The immune modulation in the epithelium is a protective feature of the epithelial function in the mucosal airways. Dysfunction of the epithelium can lead to chronic allergic airway inflammatory diseases, such as chronic rhinosinusitis with nasal polyps (CRSwNP), allergic rhinitis (AR), and allergic asthma. Chitinase-3-like-1 (CHI3L1) is a key modulator in the epithelium against irritants, pathogens, and allergens and is involved in cancers, autoimmune diseases, neurological disorders, and other chronic diseases. Induction of epithelial cell-derived CHI3L1 is also confirmed to be implicated in the pathogenesis of Th2-related airway diseases like CRSwNP, AR, and allergic asthma, triggering a cascade of subsequent inflammatory reactions leading to the disease development. The techniques that block the biological function of CHI3L1 include small interfering RNA, neutralizing antibodies, and microRNAs and these methods proved to be successful in preclinical and clinical investigation in cancers, autoimmune diseases, asthma, and chronic obstructive pulmonary disease. Therefore, treatment with CHI3L1-blocking methods could open up therapeutic options for allergic airway diseases. This review article discusses the role of epithelial cell-derived CHI3L1 in the development of CRSwNP, AR, and allergic asthma and examines the use of CHI3L1 as a potential therapeutic agent for allergic airway diseases.