LYSMD3: A mammalian pattern recognition receptor for chitin

Xin He, Brad A. Howard, Yang Liu, Aaron K. Neumann, Liwu Li, Nidhi Menon, Tiffany Roach, Shiv D. Kale, David C. Samuels, Hongyan Li, Trenton Kite, Hirohito Kita, Tony Y. Hu, Mengyao Luo, Caroline N. Jones, Uju Joy Okaa, Diane L. Squillace, Bruce S. Klein, Christopher B. Lawrence

Research output: Contribution to journalArticlepeer-review

Abstract

Chitin, a major component of fungal cell walls, has been associated with allergic disorders such as asthma. However, it is unclear how mammals recognize chitin and the principal receptor(s) on epithelial cells that sense chitin remain to be determined. In this study, we show that LYSMD3 is expressed on the surface of human airway epithelial cells and demonstrate that LYSMD3 is able to bind chitin, as well as β-glucan, on the cell walls of fungi. Knockdown or knockout of LYSMD3 also sharply blunts the production of inflammatory cytokines by epithelial cells in response to chitin and fungal spores. Competitive inhibition of the LYSMD3 ectodomain by soluble LYSMD3 protein, multiple ligands, or antibody against LYSMD3 also blocks chitin signaling. Our study reveals LYSMD3 as a mammalian pattern recognition receptor (PRR) for chitin and establishes its role in epithelial cell inflammatory responses to chitin and fungi.

Original languageEnglish (US)
Article number109392
JournalCell reports
Volume36
Issue number3
DOIs
StatePublished - Jul 20 2021

Keywords

  • Alternaria
  • LYSMD3
  • allergy
  • asthma
  • chitin
  • epithelial cell
  • innate immunity
  • pattern recognition receptor
  • β-glucan

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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