Yamasaki Sho, Ishikawa Eri, Sakuma Machie, Hara Hiromitsu, Ogata Koji, Saito Takashi
Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan.
Nat Immunol. 2008 Oct;9(10):1179-88. doi: 10.1038/ni.1651. Epub 2008 Sep 7.
Macrophage-inducible C-type lectin (Mincle) is expressed mainly in macrophages and is induced after exposure to various stimuli and stresses. Here we show that Mincle selectively associated with the Fc receptor common gamma-chain and activated macrophages to produce inflammatory cytokines and chemokines. Mincle-expressing cells were activated in the presence of dead cells, and we identified SAP130, a component of small nuclear ribonucloprotein, as a Mincle ligand that is released from dead cells. To investigate whether Mincle is required for normal responses to cell death in vivo, we induced thymocyte death by irradiating mice and found that transient infiltration of neutrophils into the thymus could be blocked by injection of Mincle-specific antibody. Our results suggest that Mincle is a receptor that senses nonhomeostatic cell death and thereby induces the production of inflammatory cytokines to drive the infiltration of neutrophils into damaged tissue.
巨噬细胞诱导性C型凝集素（Mincle）主要在巨噬细胞中表达，并在暴露于各种刺激和应激后被诱导。在此我们表明，Mincle与Fc受体共同γ链选择性结合，并激活巨噬细胞以产生炎性细胞因子和趋化因子。表达Mincle的细胞在死细胞存在的情况下被激活，并且我们鉴定出小核糖核蛋白的一个组分SAP130作为从死细胞释放的Mincle配体。为了研究Mincle在体内对细胞死亡的正常反应中是否必需，我们通过照射小鼠诱导胸腺细胞死亡，发现注射Mincle特异性抗体可阻断中性粒细胞向胸腺的短暂浸润。我们的结果表明，Mincle是一种感知非稳态细胞死亡并由此诱导炎性细胞因子产生以驱动中性粒细胞浸润到受损组织中的受体。
