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WNT-Inflammasome Signaling Mediates NOD2-Induced Development of Acute Arthritis in Mice

Singh, Vikas and Holla, Sahana and Ramachandra, Subbaraya G and Balaji, Kithiganahalli Narayanaswamy (2015) WNT-Inflammasome Signaling Mediates NOD2-Induced Development of Acute Arthritis in Mice. In: JOURNAL OF IMMUNOLOGY, 194 (7). pp. 3351-3360.

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Official URL: http://dx.doi.org/10.4049/jimmunol.1402498

Abstract

In addition to its role in innate immunity, the intracellular pathogen sensor nucleotide-binding oligomerization domain 2 (NOD2) has been implicated in various inflammatory disorders, including the development of acute arthritis. However, the molecular mechanisms involved in the development of NOD2-responsive acute arthritis are not clear. In this study, we demonstrate that NOD2 signals to a cellular protein, Ly6/PLAUR domain-containing protein 6, in a receptor-interacting protein kinase 2-TGF-beta-activated kinase 1-independent manner to activate the WNT signaling cascade. Gain- or loss-of-function of the WNT signaling pathway in an in vivo experimental mouse arthritis model or in vitro systems established the role for WNT-responsive X-linked inhibitor of apoptosis during the development of acute arthritis. Importantly, WNT-stimulated X-linked inhibitor of apoptosis mediates the activation of inflammasomes. The subsequent caspase-1 activation and IL-1 beta secretion together contribute to the phenotypic character of the inflammatory condition of acute arthritis. Thus, identification of a role for WNT-mediated inflammasome activation during NOD2 stimulation serves as a paradigm to understand NOD2-associated inflammatory disorders and develop novel therapeutics.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the AMER ASSOC IMMUNOLOGISTS, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
Keywords: OLIGOMERIZATION DOMAIN 2; RHEUMATOID-ARTHRITIS; CROHNS-DISEASE; MURINE MODEL; MURAMYL DIPEPTIDE; PLASMA-MEMBRANE; NOD2; ACTIVATION; RECOGNITION; APOPTOSIS
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Depositing User: Id for Latest eprints
Date Deposited: 28 Apr 2015 07:40
Last Modified: 28 Apr 2015 07:40
URI: http://eprints.iisc.ac.in/id/eprint/51427

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