| First Author | Sutterwala FS | Year | 2006 |
| Journal | Immunity | Volume | 24 |
| Issue | 3 | Pages | 317-27 |
| PubMed ID | 16546100 | Mgi Jnum | J:113333 |
| Mgi Id | MGI:3665414 | Doi | 10.1016/j.immuni.2006.02.004 |
| Citation | Sutterwala FS, et al. (2006) Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1. Immunity 24(3):317-27 |
| abstractText | Mutations in the NALP3/CIAS1/cryopyrin gene are linked to three autoinflammatory disorders: Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and chronic infantile neurologic cutaneous and articular syndrome. NALP3, with the adaptor molecule ASC, has been proposed to form a caspase-1-activating 'inflammasome,' a complex with pro-IL1beta-processing activity. Here, we demonstrate the effect of NALP3 deficiency on caspase-1 function. NALP3 was essential for the ATP-driven activation of caspase-1 in lipopolysaccharide-stimulated macrophages and for the efficient secretion of the caspase-1-dependent cytokines IL-1alpha, IL-1beta, and IL-18. IL-1beta has been shown to play a key role in contact hypersensitivity; we show that ASC- and NALP3-deficient mice also demonstrate an impaired contact hypersensitivity response to the hapten trinitrophenylchloride. NALP3, however, was not required for caspase-1 activation by Salmonella typhimurium, and NALP3 deficiency only partially protects mice from the lethal effects of endotoxin. These data suggest that NALP3 plays a specific role in the caspase-1 activation pathway. |
