title: AMCase is a crucial regulator of type 2 immune responses to inhaled house dust mites.
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.
authors.affiliation: Department of Immunobiology.
authors.forename: Lark Kyun
authors.initials: LK
authors.lastname: Kim
authors.affiliation: Department of Immunobiology.
authors.forename: Rimpei
authors.initials: R
authors.lastname: Morita
authors.affiliation: Department of Immunobiology.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Immunobiology, Department of Laboratory Medicine.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Eisenbarth
authors.affiliation: Section of Pulmonary and Critical Care Medicine, and.
authors.forename: Chun Geun
authors.initials: CG
authors.lastname: Lee
authors.affiliation: Section of Pulmonary and Critical Care Medicine, and.
authors.forename: Jack
authors.initials: J
authors.lastname: Elias
authors.affiliation: Department of Immunobiology.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Eynon
authors.affiliation: Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520 richard.flavell@yale.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000469:parasitology* / Q000517:prevention & control*; D015153:Blotting, Western; D002688:Chitinases / Q000235:genetics / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D055879:Gene Knock-In Techniques; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology; D051379:Mice; D016133:Polymerase Chain Reaction; D039981:Pyroglyphidae / Q000276:immunology*
chemical_list: D017931:DNA Primers; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; C499255:AMCase, mouse; D002688:Chitinases
keywords: AMCase; IL-33; chitin; house dust mite