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Inflammation

Cytokine ignition complex characterized

Nature Reviews Immunology volume 4, page 320 (2004)Cite this article

The genetic defect in patients with Muckle-Wells syndrome — a severe inflammatory disorder that can be treated with an interleukin-1 (IL-1) receptor antagonist — is found in the gene encoding NALP3. Now, work from Jürg Tschopp's laboratory, published in Immunity, has provided a molecular mechanism by which NALP3 influences the production of IL-1β.

The CARD-containing region of NALP1 is missing in the other NALP-family members. The authors therefore investigated whether Cardinal, a protein with structural homology to the missing segment, could interact with other NALP proteins, and found that Cardinal co-immunoprecipitated with both NALP2 and NALP3. NALP2 and NALP3 were also shown to associate with ASC, and the CARD of Cardinal was shown to associate with caspase-1. These results indicate that NALP3 could form an inflammasome — consisting of ASC, Cardinal and caspase-1 — capable of processing pro-IL-1β (see figure).

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ORIGINAL RESEARCH PAPER

  1. Agostini, L. et al. NALP3 forms an IL-1β-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity 20, 319–325 (2004)

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Authors
  1. Karen Honey
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Honey, K. Cytokine ignition complex characterized. Nat Rev Immunol 4, 320 (2004). https://doi.org/10.1038/nri1357

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  • DOI: https://doi.org/10.1038/nri1357

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