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Immunity. 2018 Jul 17;49(1):56-65.e4. doi: 10.1016/j.immuni.2018.04.032. Epub 2018 Jun 26.

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

Author information

1
Department of Pharmacology and the Center for Lung and Vascular Biology, The University of Illinois College of Medicine, Chicago, IL 60612, USA.
2
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
3
Department of Pharmacology and the Center for Lung and Vascular Biology, The University of Illinois College of Medicine, Chicago, IL 60612, USA. Electronic address: abmalik@uic.edu.

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 (K2P) 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.

KEYWORDS:

KCNK6; NLRP3 inflammasome; P2X7 receptor; TWIK2; inflammation; potassium channel

PMID:
29958799
PMCID:
PMC6051907
[Available on 2019-07-17]
DOI:
10.1016/j.immuni.2018.04.032

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