AMCase is a crucial regulator of type 2 immune responses to inhaled house dust mites

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Authors: Lark Kyun Kim ; Rimpei Morita ; Yasushi Kobayashi ; Stephanie C. Eisenbarth ; Chun Geun Lee ; Jack Elias ; Elizabeth E. Eynon ; Richard A. Flavell

Citation: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.112(22) : 2891-2899, 2015

Journal Title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

MeSH: Animals ; Asthma/immunology* ; Asthma/parasitology* ; Asthma/prevention & control* ; Blotting, Western ; Chitinases/genetics ; Chitinases/immunology* ; DNA Primers/genetics ; Disease Models, Animal* ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Gene Knock-In Techniques ; Interleukin-33 ; Interleukins/immunology ; Mice ; Polymerase Chain Reaction ; Pyroglyphidae/immunology*

Abstract: Chitinases are enzymes that cleave chitin, a component of the exoskeleton of many organisms including the house dust mite (HDM). Here we show that knockin mice expressing an enzymatically inactive acidic mammalian chitinase (AMCase), the dominant true chitinase in mouse lung, showed enhanced type 2 immune responses to inhaled HDM. We found that uncleaved chitin promoted the release of IL-33, whereas cleaved chitin could be phagocytosed and could induce the activation of caspase-1 and subsequent activation of caspase-7; this results in the resolution of type 2 immune responses, probably by promoting the inactivation of IL-33. These data suggest that AMCase is a crucial regulator of type 2 immune responses to inhaled chitin-containing aeroallergens.