The concept of the inflammasome and its rheumatologic implications.
The inflammasome is a proteolytic complex that regulates IL1β and IL-18 secretion in macrophages and dendritic cells. Its plays a vital role in the control of the inflammatory and cellular responses to infectious and danger signals and is an essential part of the innate immune system. Four different inflammasomes have been identified so far, and the NLRP3-inflammasome has been the best-studied in relation to human disease. Activation of the NLRP3-inflammasome by microcrystals, such as monosodium urate (MSU) and basic calcium phosphate (BCP) crystals, leads to IL1β release, which in turn triggers local inflammation. Dysfunction of the NLRP3-inflammasome due to mutations of the NLRP3 gene is the cause of the auto-inflammatory syndrome CAPS. The symptoms and signs of inflammation in both conditions respond to IL1 blockade. IL1 inhibitors have also been used successfully in other idiopathic inflammatory diseases, suggesting that dysregulated inflammasome activity contributes to the pathogenesis of multiple diseases, but the precise underlying mechanisms remain to be identified.
Service de rhumatologie, université de Lausanne, CHU Vaudois, avenue Pierre-Decker 4, 1011 Lausanne, Suisse. Electronic address: alexanderkai-lik.so@chuv.ch.
Alexander
A
So
Service de rhumatologie, université de Lausanne, CHU Vaudois, avenue Pierre-Decker 4, 1011 Lausanne, Suisse.
Nathalie
N
Busso
D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology*; D002352:Carrier Proteins; D003713:Dendritic Cells / Q000276:immunology; D006073:Gout / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D058847:Inflammasomes / Q000276:immunology / Q000502:physiology*; D008264:Macrophages / Q000276:immunology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012216:Rheumatic Diseases / Q000276:immunology / Q000503:physiopathology*
D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human
Auto-inflammatory disorders; Gout; IL1β; Inflammasome