TWIK2 钾离子外流通道在巨噬细胞中介导 NLRP3 炎性小体诱导的炎症反应。
The TWIK2 Potassium Efflux Channel in Macrophages Mediates NLRP3 Inflammasome-Induced Inflammation.
机构信息
Department of Pharmacology and the Center for Lung and Vascular Biology, The University of Illinois College of Medicine, Chicago, IL 60612, USA.
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
出版信息
Immunity. 2018 Jul 17;49(1):56-65.e4. doi: 10.1016/j.immuni.2018.04.032. Epub 2018 Jun 26.
Abstract
Potassium (K) efflux across the plasma membrane is thought to be an essential mechanism for ATP-induced NLRP3 inflammasome activation, yet the identity of the efflux channel has remained elusive. Here we identified the two-pore domain K channel (K) TWIK2 as the K efflux channel triggering NLRP3 inflammasome activation. Deletion of Kcnk6 (encoding TWIK2) prevented NLRP3 activation in macrophages and suppressed sepsis-induced lung inflammation. Adoptive transfer of Kcnk6 macrophages into mouse airways after macrophage depletion also prevented inflammatory lung injury. The K efflux channel TWIK2 in macrophages has a fundamental role in activating the NLRP3 inflammasome and consequently mediates inflammation, pointing to TWIK2 as a potential target for anti-inflammatory therapies.
摘要
钾（K）跨质膜外流被认为是 ATP 诱导 NLRP3 炎性体激活的一个必要机制，但外流通道的身份仍然难以捉摸。在这里，我们鉴定出双孔域钾通道（K）TWIK2 是触发 NLRP3 炎性体激活的 K 外流通道。Kcnk6（编码 TWIK2）的缺失阻止了巨噬细胞中 NLRP3 的激活，并抑制了脓毒症引起的肺部炎症。巨噬细胞耗竭后，将 Kcnk6 巨噬细胞过继转移到小鼠气道中也可防止炎症性肺损伤。巨噬细胞中的 K 外流通道 TWIK2 在激活 NLRP3 炎性体方面起着基础性作用，从而介导炎症，表明 TWIK2 是抗炎治疗的潜在靶点。
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