<figcaption> Credit: Nevit Dilmen / Wikimedia Commons</figcaption>
Credit: Nevit Dilmen / Wikimedia Commons

The paper: S. Mariathasan et al., "Cryopyrin activates the inflammasome in response to toxins and ATP," Nature, 440:228-32, 2006. (Cited in 121 papers)

The finding: By observing mice deficient in the adaptor protein cryopyrin, Vishva Dixit of Genentech and his colleagues discovered cryopyrin's role in activating the inflammasome, a complex of proteins essential for the innate immune response. Cryopyrin, also known as NALP3, causes the release of the cytokines interleukin (IL)-1β and IL-18.

The significance: Mutations in cryopyrin/NALP3 were known to be associated with autoinflammatory diseases characterized by the excessive production of IL-1β. "We knew NALP3 was really important," says Emma Creagh of Trinity College in Dublin, "but we didn't know exactly how." Dixit's findings identified a critical step.

The question: "We don't know what resides between membrane disruption and activation [of the inflammasome] by cryopyrin," says Dixit. Several groups are trying to...

IL-1β release (pg/ml)

Stress stimulus with LPS* endotoxin Control Cryopyrin knockout
LPS + ATP 2,113 199
LPS + Nigericin (potassium transporter) 6,175 55
LPS + Maitotoxin (membrane disruptor) 751 50

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