The TWIK2 Potassium Efflux Channel in Macrophages Mediates NLRP3 Inflammasome-Induced Inflammation.

Immunity 2018 07 26;49(1):56-65.e4. Epub 2018 Jun 26.

Department of Pharmacology and the Center for Lung and Vascular Biology, The University of Illinois College of Medicine, Chicago, IL 60612, USA. Electronic address:

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.

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http://dx.doi.org/10.1016/j.immuni.2018.04.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051907PMC
July 2018
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