| First Author | Nakamura Y | Year | 2012 |
| Journal | Immunity | Volume | 37 |
| Issue | 1 | Pages | 85-95 |
| PubMed ID | 22819042 | Mgi Jnum | J:187396 |
| Mgi Id | MGI:5436355 | Doi | 10.1016/j.immuni.2012.04.013 |
| Citation | Nakamura Y, et al. (2012) Critical role for mast cells in interleukin-1beta-driven skin inflammation associated with an activating mutation in the nlrp3 protein. Immunity 37(1):85-95 |
| abstractText | Cryopyrin-associated periodic syndromes (CAPS) are caused by aberrant interleukin-1beta (IL-1beta) production induced by mutations in the NLRP3 protein in humans, but the mechanisms involved remain poorly understood. Using a mouse model, we show a role for the indigenous microbiota and mast cells (MCs) in skin disease associated with mutant Nlrp3 protein. Unlike normal cells, MCs expressing mutant Nlrp3 produced IL-1beta in response to lipopolysaccharide or tumor necrosis factor-alpha (TNF-alpha). In neonatal mice, the microbiota induced TNF-alpha and IL-1beta and promoted skin disease. MC deficiency greatly reduced disease in Nlrp3 mutant mice, and reconstitution of MC-deficient mice with mutant MCs restored skin disease, which required the expression of IL-1beta in MCs. Surprisingly, neutralization of TNF-alpha abrogated IL-1beta production and skin disease in neonatal Nlrp3 mutant mice, but not in affected adult mice. Thus, the microbiota and MCs initiate cellular events leading to dysregulated IL-1beta production and skin inflammation in neonatal mice with the CAPS-associated Nlrp3 mutation. |
