LYSMD3: A mammalian pattern recognition receptor for chitin

Autor: He, Xin, Howard, Brad A., Liu, Yang, Neumann, Aaron K., Li, Liwu, Menon, Nidhi, Roach, Tiffany, Kale, Shiv D., Samuels, David C., Li, Hongyan, Kite, Trenton, Kita, Hirohito, Hu, Tony Y., Luo, Mengyao, Jones, Caroline N., Okaa, Uju Joy, Squillace, Diane L., Klein, Bruce S., Lawrence, Christopher B.
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Popis: 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 beta-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 ecto-domain 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. NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01AI130411, R21AI115986] Published version This work was supported by NIH R21AI115986 to C.B.L. and L.L. and by NIH R01AI130411 to B.S.K. The Graphical abstract was created with BioRender. com.
Databáze: OpenAIRE