WNT-inflammasome signaling mediates NOD2-induced development of acute arthritis in mice

Singh, Vikas ; Holla, Sahana ; Subbaraya, G. Ramachandra ; Balaji, Kithiganahalli Narayanaswamy (2015) WNT-inflammasome signaling mediates NOD2-induced development of acute arthritis in mice The Journal of Immunology, 194 (7). pp. 3351-3360. ISSN 0022-1767

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Official URL: http://www.jimmunol.org/content/194/7/3351.long

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


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-β-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-1Β 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:Article
Source:Copyright of this article belongs to American Association of Immunologists.
ID Code:99567
Deposited On:26 Nov 2016 11:49
Last Modified:26 Nov 2016 11:49

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