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Review
. 2010 Sep;122(5):125-33.
doi: 10.3810/pgm.2010.09.2209.

Inflammasome-mediated autoinflammatory disorders

Shruti P Wilson  1 , Suzanne L Cassel
Affiliations
Review

Inflammasome-mediated autoinflammatory disorders

Shruti P Wilson et al. Postgrad Med. 2010 Sep.

Abstract

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.

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Figures

Figure 1
Figure 1
A. Domain structures of selected NLR molecules, the common adaptor ASC and the effector molecule caspase-1. (PYD – Pyrin Domain; NACHT – domain present in Naip, CIITA, HET-E and TP-1; LRR – Leucine Rich Repeat; CARD – caspase recruitment domain; FIIND – domain with function to find; P20/P10 – subunits of caspase-1) B. Model of NLRP3 inflammasome assembly. Activation of NLRP3 via binding of its unknown ligand to the LRR allows binding of its PYD to the PYD of ASC. The CARD of ASC associates with the CARD of inactive caspase-1, driving its activation and resultant self-cleavage. The resultant active caspase-1 cleaves pro-IL-1β to active and secreted IL-1β.
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References

    1. McDermott MF, Aksentijevich I. The autoinflammatory syndromes. Curr Opin Allergy Clin Immunol. 2002;2:511–516. - PubMed
    1. McGonagle D, McDermott MF. A proposed classification of the immunological diseases. PLoS Med. 2006;3:e297. - PMC - PubMed
    1. Janeway CA, Jr, Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002;20:197–216. - PubMed
    1. Jones JD, Dangl JL. The plant immune system. Nature. 2006;444:323–329. - PubMed
    1. Ye Z, Ting JP. NLR, the nucleotide-binding domain leucine-rich repeat containing gene family. Curr Opin Immunol. 2008;20:3–9. - PubMed

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