机构：[1]Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, USA[2]Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI 53706, USA[3]Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112, USA[4]Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300060, China[5]Department of Pathology, University of New Mexico, Albuquerque, NM 87131, USA[6]Graduate Program in Translational Biology, Medicine, and Health, Virginia Tech, Blacksburg, VA 24061, USA[7]Nutritional Immunology and Molecular Medicine Institute, Blacksburg, VA 24060, USA[8]Department of Molecular Physiology and Biophysics, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN 37232, USA[9]Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China外科系统普通外科首都医科大学宣武医院[10]Fralin Life Sciences Institute, Virginia Tech, Blacksburg, VA 24061, USA[11]Department of Immunology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA[12]Department of Bioengineering, University of Texas, Dallas, TX 75080, USA[13]Department of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA[14]Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA[15]Greenlight Biosciences, Research Triangle Park, Suite 1250, Durham, NC 27709, USA
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.
基金：
NIHUnited States Department of Health & Human Services National Institutes of Health (NIH) - USA [R01AI130411, R21AI115986]
第一作者机构：[1]Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, USA[2]Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI 53706, USA
通讯作者：
通讯机构：[1]Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, USA[2]Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI 53706, USA[13]Department of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA[14]Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA[15]Greenlight Biosciences, Research Triangle Park, Suite 1250, Durham, NC 27709, USA
推荐引用方式(GB/T 7714)：
He Xin,Howard Brad A.,Liu Yang,et al.LYSMD3: A mammalian pattern recognition receptor for chitin[J].CELL REPORTS.2021,36(3):doi:10.1016/j.celrep.2021.109392.
APA：
He, Xin,Howard, Brad A.,Liu, Yang,Neumann, Aaron K.,Li, Liwu...&Lawrence, Christopher B..(2021).LYSMD3: A mammalian pattern recognition receptor for chitin.CELL REPORTS,36,(3)
MLA：
He, Xin,et al."LYSMD3: A mammalian pattern recognition receptor for chitin".CELL REPORTS 36..3(2021)
生物