| First Author | Stackowicz J | Year | 2021 |
| Journal | J Exp Med | Volume | 218 |
| Issue | 10 | PubMed ID | 34477811 |
| Mgi Jnum | J:327490 | Mgi Id | MGI:7261120 |
| Doi | 10.1084/jem.20201466 | Citation | Stackowicz J, et al. (2021) Neutrophil-specific gain-of-function mutations in Nlrp3 promote development of cryopyrin-associated periodic syndrome. J Exp Med 218(10):e20201466 |
| abstractText | 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-1beta. However, the specific myeloid cell population(s) exhibiting inflammasome activity and sustained IL-1beta 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-1beta. Together, our data indicate that neutrophils, rather than MCs, can represent the main cellular drivers of CAPS pathology. |
