Thioredoxin-interacting protein links oxidative stress to inflammasome activation

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Title
Thioredoxin-interacting protein links oxidative stress to inflammasome activation
Author(s)
R Zhou; A Tardivel; B Thorens; In Pyo Choi; J Tschopp
Bibliographic Citation
Nature Immunology, vol. 11, no. 2, pp. 136-140
Publication Year
2010
Abstract
The NLRP3 inflammasome has a major role in regulating innate immunity. Deregulated inflammasome activity is associated with several inflammatory diseases, yet little is known about the signaling pathways that lead to its activation. Here we show that NLRP3 interacted with thioredoxin (TRX)-interacting protein (TXNIP), a protein linked to insulin resistance. Inflammasome activators such as uric acid crystals induced the dissociation of TXNIP from thioredoxin in a reactive oxygen species (ROS)-sensitive manner and allowed it to bind NLRP3. TXNIP defficiency impaired activation of the NLRP3 inflammasome and subsequent secretion of interleukin 1Β (IL-1Β). Akin to Txnip/ mice, Nlrp3/ mice showed improved glucose tolerance and insulin sensitivity. The participation of TXNIP in the NLRP3 inflammasome activation may provide a mechanistic link to the observed involvement of IL-1Β in the pathogenesis of type 2 diabetes.
ISSN
1529-2908
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/ni.1831
Type
Article
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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