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Inflammasome-independent IL-1β mediates autoinflammatory disease in Pstpip2-deficient mice

2014; National Academy of Sciences; Volume: 111; Issue: 3 Linguagem: Inglês

10.1073/pnas.1318685111

1091-6490

Suzanne L. Cassel, John R. Janczy, Xinyu Bing, Shruti P. Wilson, Alicia K. Olivier, Jesse E. Otero, Yoichiro Iwakura, Dmitry M. Shayakhmetov, Alexander G. Bassuk, Yousef Abu‐Amer, Kim A. Brogden, Trudy L. Burns, Fayyaz S. Sutterwala, Polly J. Ferguson,

Spondyloarthritis Studies and Treatments

Significance Chronic recurrent multifocal osteomyelitis (CRMO) is a human disorder of the innate immune system that causes bone inflammation that mimics infectious osteomyelitis. There is a spontaneous mutant mouse model of the disease that is caused by homozygous mutations in the gene Pstpip2 . Our studies show that bone inflammation in this model is mediated by the cytokine IL-1β, but that the disease is independent of the nucleotide-binding domain, leucine-rich repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome and caspase-1, which is different from most other IL-1–mediated disorders. Further, we implicate neutrophils and neutrophil serine proteases in disease pathogenesis. These data provide a rationale for directly targeting the IL-1 receptor or IL-1β as a therapeutic strategy in CRMO.