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, USA.
Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, USA.
Cell Rep. 2021 Jul 20;36(3):109392. doi: 10.1016/j.celrep.2021.109392.
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.
几丁质是真菌细胞壁的主要成分，与哮喘等过敏疾病有关。然而，哺乳动物如何识别几丁质以及感知几丁质的上皮细胞的主要受体仍有待确定。在这项研究中，我们表明 LYSMD3 表达在人呼吸道上皮细胞的表面，并证明 LYSMD3 能够结合真菌细胞壁上的几丁质和β-葡聚糖。LYSMD3 的敲低或敲除也显著削弱了上皮细胞对几丁质和真菌孢子的反应产生炎症细胞因子的能力。可溶性 LYSMD3 蛋白、多种配体或针对 LYSMD3 的抗体对 LYSMD3 外显子的竞争性抑制也阻断了几丁质信号。我们的研究揭示了 LYSMD3 作为几丁质的哺乳动物模式识别受体 (PRR)，并确立了它在上皮细胞对几丁质和真菌的炎症反应中的作用。
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