2018
DOI: 10.1016/j.immuni.2018.04.032
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The TWIK2 Potassium Efflux Channel in Macrophages Mediates NLRP3 Inflammasome-Induced Inflammation

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 macr… Show more

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Cited by 293 publications
(287 citation statements)
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“…To this end, we depleted AMs in WT and PAR2-null mice by injecting clodronate liposomes intracheal ( i.t. ) and after 48 h adoptively transferred WT or PAR2-null bone-marrow-derived macrophages (BMDMs) into WT or PAR2-null mice, respectively (Di et al, 2018), and determined lung injury following LPS challenge (Figure 2B). We observed that adoptive transfer of WT-BMDMs (+/+) in PAR2-null lungs resolved lung edema and reduced BAL-inflammatory cytokines (Figures 2C and 2D).…”
Section: Resultsmentioning
confidence: 99%
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“…To this end, we depleted AMs in WT and PAR2-null mice by injecting clodronate liposomes intracheal ( i.t. ) and after 48 h adoptively transferred WT or PAR2-null bone-marrow-derived macrophages (BMDMs) into WT or PAR2-null mice, respectively (Di et al, 2018), and determined lung injury following LPS challenge (Figure 2B). We observed that adoptive transfer of WT-BMDMs (+/+) in PAR2-null lungs resolved lung edema and reduced BAL-inflammatory cytokines (Figures 2C and 2D).…”
Section: Resultsmentioning
confidence: 99%
“…The depletion was followed by reconstitution, at 48 h, using 1×10 6 BMDM for each mouse. The cells were injected by non-invasive intratracheal instillation method (Di et al, 2018). Briefly, the mouse was suspended in a semi-recumbent position on a solid support.…”
Section: Methodsmentioning
confidence: 99%
“…Furthermore, to maintain physiological relevance, movement of other ions was not blocked during these measurements as described earlier by Di et al [20]. Furthermore, to maintain physiological relevance, movement of other ions was not blocked during these measurements as described earlier by Di et al [20].…”
Section: Cellular Cholesterol Levels Modulate K + Channel Activity Inmentioning
confidence: 74%
“…Furthermore, to maintain physiological relevance, no channel selective inhibitors were used to isolate ion fluxes through any particular channel as described by Di et al [20] to identify TWIK2 or Kcnk6 as the K + channel involved in macrophage K + efflux. Junction potentials were corrected and a 3 M KClagar bridge served as the ground electrode.…”
Section: Measurement Of K + Currentsmentioning
confidence: 99%
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