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

Publication date: Available online 26 June 2018

Source: Immunity

Author(s): Anke Di, Shiqin Xiong, Zhiming Ye, R.K. Subbarao Malireddi, Satoshi Kometani, Ming Zhong, Manish Mittal, Zhigang Hong, Thirumala-Devi Kanneganti, Jalees Rehman, Asrar B. Malik

Summary

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_2P) 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.

Graphical Abstract

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