Details

Autor(en) / Beteiligte

• Stackowicz, Julien
• Gaudenzio, Nicolas
• Serhan, Nadine
• Conde, Eva
• Godon, Ophélie
• Marichal, Thomas
• Starkl, Philipp
• Balbino, Bianca
• Roers, Axel
• Bruhns, Pierre
• Jönsson, Friederike
• Moguelet, Philippe
• Georgin-Lavialle, Sophie
• Broderick, Lori
• Hoffman, Hal M
• Galli, Stephen J
• Reber, Laurent L

Titel

Neutrophil-specific gain-of-function mutations in Nlrp3 promote development of cryopyrin-associated periodic syndrome

Ist Teil von

• The Journal of experimental medicine, 2021-10, Vol.218 (10)

Ort / Verlag

United States: Rockefeller University Press

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Gain-of-function mutations in NLRP3 are responsible for a spectrum of autoinflammatory diseases collectively referred to as "cryopyrin-associated periodic syndromes" (CAPS). Treatment of CAPS patients with IL-1-targeted therapies is effective, confirming a central pathogenic role for IL-1β. However, the specific myeloid cell population(s) exhibiting inflammasome activity and sustained IL-1β production in CAPS remains elusive. Previous reports suggested an important role for mast cells (MCs) in this process. Here, we report that, in mice, gain-of-function mutations in Nlrp3 restricted to neutrophils, and to a lesser extent macrophages/dendritic cells, but not MCs, are sufficient to trigger severe CAPS. Furthermore, in patients with clinically established CAPS, we show that skin-infiltrating neutrophils represent a substantial biological source of IL-1β. Together, our data indicate that neutrophils, rather than MCs, can represent the main cellular drivers of CAPS pathology.