Abstract
Background: The house dust mite (HDM) is the most common cause of
allergic diseases, and TLR4 acts as an overarching receptor for allergic
responses. This study aimed to identify novel allergen binding to TLR4
in HDMs and unveil its unique role in allergic responses. Methods: Der p
38 was purified and characterized by LC-MS/MS-based peptide mapping.
Biolayer interferometry and structure modeling unveiled TLR4-binding
activity and the structure of recombinant Der p 38. The allergenicity of
Der p 38 was confirmed by a skin prick test, and basophil activation and
dot blot assays. Results: The skin prick test identified 24 out of 45
allergic subjects (53.3%) as Der p 38-positive subjects. Der p
38-augmented CD203c expression was noted in the basophils of Der p
38-positive allergic subjects. In animal experiments, Der p 38
administration induced the infiltration of neutrophils as well as
eosinophils and exhibited clinical features similar to asthma via TLR4
activation. Persistent Der p 38 administration induced severe neutrophil
inflammation. Der p 38 enhanced cytokine production in human bronchial
epithelial cells, which inhibited apoptosis in neutrophils and
eosinophils. The mechanisms involved LYN, PI3K, AKT, ERK, and NF-κB.
Conclusions: These findings showed that Der p 38 is a bridge allergen
between eosinophilic and neutrophilic inflammation, and contribute to
understanding the TLR4-mediated complex pathogenesis of allergic
diseases.