Research ArticleInflammation

Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation

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Science Translational Medicine  30 Mar 2016:
Vol. 8, Issue 332, pp. 332ra45
DOI: 10.1126/scitranslmed.aaf1471

Guarding inflammation

The innate immune system is hard-wired to protect people from infection. However, mutations in these protective genes can lead to uncontrolled inflammation, resulting in autoinflammatory disease. Now, Masters et al. describe a family with an autoinflammatory disease caused by a previously unreported mutation in pyrin. This mutation disrupts pyrin regulation and mimics the effect of pathogen sensing by pyrin, leading to proinflammatory interleukin-1β (IL-1β) production. Indeed, targeting IL-1β resolved disease in one patient. These data suggest that pyrin is regulated through a guard-like mechanism, which guards against autoinflammation in humans.

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