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

Research output: Contribution to journalArticle

28 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 languageEnglish
Pages (from-to)E2891-E2899
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number22
DOIs
Publication statusPublished - 2015 Jun 2

Keywords

  • AMCase
  • Chitin
  • House dust mite
  • IL-33

ASJC Scopus subject areas

  • General

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    Kim, L. K., Morita, R., Kobayashi, Y., Eisenbarth, S. C., Lee, C. G., Elias, J., Eynon, E. E., & Flavell, R. A. (2015). AMCase is a crucial regulator of type 2 immune responses to inhaled house dust mites. Proceedings of the National Academy of Sciences of the United States of America, 112(22), E2891-E2899. https://doi.org/10.1073/pnas.1507393112