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

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

doi:10.1073/pnas.1507393112

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

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

Department of Microbiology and Immunology

Research output: Contribution to journal › Article › peer-review

47 Citations (Scopus)

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.

Original language	English
Pages (from-to)	E2891-E2899
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	112
Issue number	22
DOIs	https://doi.org/10.1073/pnas.1507393112
Publication status	Published - 2015 Jun 2

Keywords

AMCase
Chitin
House dust mite
IL-33

ASJC Scopus subject areas

General

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10.1073/pnas.1507393112

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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.",

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AU - Kim, Lark Kyun

AU - Morita, Rimpei

AU - Kobayashi, Yasushi

AU - Eisenbarth, Stephanie C.

AU - Lee, Chun Geun

AU - Elias, Jack

AU - Eynon, Elizabeth E.

AU - Flavell, Richard A.

PY - 2015/6/2

Y1 - 2015/6/2

N2 - 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.

AB - 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.

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KW - House dust mite

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

Abstract

Keywords

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