LYSMD3: A mammalian pattern recognition receptor for chitin.
LYSMD3: A mammalian pattern recognition receptor for chitin.
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DOI：
10.1016/j.celrep.2021.109392
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发表时间：
2021-07-20
期刊：
影响因子：
8.8
通讯作者：
Lawrence CB
中科院分区：
文献类型：
--
作者：
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
几丁质是真菌细胞壁的主要成分，与过敏性疾病如哮喘有关。然而，目前还不清楚哺乳动物如何识别几丁质和上皮细胞上的主要受体，感觉几丁质仍有待确定。在这项研究中，我们发现LYSMD 3在人气道上皮细胞表面表达，并证明LYSMD 3能够结合真菌细胞壁上的几丁质和β-葡聚糖。LYSMD 3的敲除或敲除也显著减弱了上皮细胞响应几丁质和真菌孢子而产生的炎性细胞因子。可溶性LYSMD 3蛋白、多配体或针对LYSMD 3的抗体对LYSMD 3胞外域的竞争性抑制也阻断几丁质信号传导。我们的研究揭示了LYSMD 3作为哺乳动物模式识别受体（PRR）的几丁质，并建立其在上皮细胞炎症反应几丁质和真菌的作用。哺乳动物几丁质识别知之甚少，但意义重大，因为几丁质是无处不在的，并与疾病。在这里，He等人揭示了人肺上皮细胞上的LYSMD 3与几丁质和真菌孢子结合并介导细胞因子的产生。他们发现LYSMD 3也能够结合β-葡聚糖。
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. Mammalian chitin recognition is poorly understood but significant because chitin is ubiquitous and linked to disease. Here, He et al. reveal that LYSMD3 on human lung epithelial cells binds to chitin and fungal spores and mediates production of cytokines. They find that LYSMD3 is also able to bind β-glucan.
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