Despite the lack of endogenous chitin synthesis, mammalian genomes encode two enzymatically active true chitinases (chitotriosidase and acidic mammalian chitinase) and a variable number of chitinase-like proteins (CLPs) that have no enzyme activity but bind chitin. Chitinases and CLPs are prominent components of type-2 immune response-mediated respiratory diseases. However, despite extensive research into their role in allergic airway disease, there is still no agreement on whether they are mere biomarkers of disease or actual disease drivers. Functions ascribed to chitinases and CLPs include, but are not limited to host defense against chitin-containing pathogens, directly promoting inflammation, and modulating tissue remodeling and fibrosis. Here, we discuss in detail the chitin-dependent and -independent roles of chitinases and CLPs in the context of allergic airway disease, and recent advances and emerging concepts in the field that might identify opportunities for new therapies.

alternatively activated macrophage

acidic mammalian chitinase

bronchoalveolar lavage

chitinase-like protein

chronic obstructive pulmonary disease

damage-associated molecular pattern

family 18 of glycosyl hydrolases

N-acetyl-glucosamine

pathogen-associated molecular pattern

pattern recognition receptor

Chitinases

Chitinase-like proteins

Chitin

Asthma

Allergic airway disease

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