Inflammasome-mediated autoinflammatory disorders.

The nucleotide-binding domain leucine-rich repeat containing (NLR) family of receptors are members of the innate immune system, and have a critical role in host defense. These molecules are key to driving inflammatory responses to abnormal cellular conditions. Many NLRs serve this role on activation by forming a multiprotein complex called an inflammasome. The inflammasome drives the processing and release of cytokines, such as the proinflammatory cytokines interleukin (IL)-1β and IL-18. Recently, the important function of NLR molecules in autoinflammatory disorders has been recognized, in part through the identification of the role of IL-1β in the pathogenesis of several autoinflammatory diseases. Cryopyrin-associated periodic syndromes were the first autoinflammatory disorders found to be directly mediated by dysfunctional inflammasome activation. This finding has subsequently led to studies in both murine models and humans that have revealed several other inflammatory conditions associated with activation of NLR-containing inflammasomes. Understanding the molecular pathophysiology of these autoinflammatory disorders has further guided the successful development of targeted therapy against IL-1. In this review, we provide an overview of the inflammasomes and describe the important role they play in the development and manifestation of autoinflammatory diseases.