Research ArticleCELL DEATH

Gasdermin D plays a vital role in the generation of neutrophil extracellular traps

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Science Immunology  24 Aug 2018:
Vol. 3, Issue 26, eaar6689
DOI: 10.1126/sciimmunol.aar6689

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Casting NETs

Gasdermin D (GSDMD), a pore-forming protein, has emerged as a key downstream effector in pyroptosis, a form of cell death induced by intracellular lipopolysaccharide (LPS). Here, Sollberger et al. demonstrate that GSDMD is activated in neutrophils, during the generation of neutrophil extracellular traps (NETs). NETs are composed of chromatin and antimicrobial proteins and are cast by dying neutrophils in a process termed NETosis. While carrying out a chemical screen to identify molecules that block NETosis, Sollberger et al. identified a pyrazolo-oxazepine scaffold–based molecule that binds GSDMD to be an inhibitor of NETosis. In the same issue, Chen et al. also report a role for GSDMD in NETosis, and Rathkey et al. report necrosulfonamide to be an inhibitor of GSDMD.