LYSMD3: A Mammalian Pattern Recognition Receptor for Chitin

Authors

• Xin He, Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, USA; Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USAFollow
• Brad A. Howard, Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, USA
• Yang Liu, Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112, USA; Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300060, China
• Aaron K. Neumann, Department of Pathology, University of New Mexico, Albuquerque, NM 87131, USA
• Liwu Li, Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, USA
• Nidhi Menon, Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, USA; Graduate Program in Translational Biology, Medicine, and Health, Virginia Tech, Blacksburg, VA 24061, USA
• Tiffany Roach, Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, USA
• Shiv D. Kale, Nutritional Immunology and Molecular Medicine Institute, Blacksburg, VA 24060, USA
• David C. Samuels, Department of Molecular Physiology and Biophysics, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN 37232, USA
• Hongyan Li, Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
• Trenton Kite, Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, USA; Fralin Life Sciences Institute, Virginia Tech, Blacksburg, VA 24061, USA
• Hirohito Kita, Department of Immunology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA
• Tony Y. Hu, Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112, USA
• Mengyao Luo, Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, USA
• Caroline N. Jones, Department of Bioengineering, University of Texas, Dallas, TX 75080, USA
• Uju Joy Okaa, Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA
• Diane L. Squillace, Department of Immunology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA
• Bruce S. Klein, Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USAFollow
• Christopher B. Lawrence, Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, USAFollow

Document Type

Article

Publication Date

7-20-2021

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.

Recommended Citation

He X, Howard BA, Liu Y, Neumann AK, Li L, Menon N, Roach T, Kale SD, Samuels DC, Li H, Kite T, Kita H, Hu TY, Luo M, Jones CN, Okaa UJ, Squillace DL, Klein BS, Lawrence CB. LYSMD3: A mammalian pattern recognition receptor for chitin. Cell Rep. 2021 Jul 20;36(3):109392. doi: 10.1016/j.celrep.2021.109392. PMID: 34289364; PMCID: PMC8344708.