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Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease
journal contribution
posted on 2023-06-07, 16:00 authored by Kim Midwood, Sandra SacreSandra Sacre, Anna M Piccinini, Julia Inglis, Annette Trebaul, Emma Chan, Stefan Drexler, Nidhi Sofat, Masahide Kashiwagi, Gertraud Orend, Fionula Brennan, Brian FoxwellAlthough there have been major advances in the treatment of rheumatoid arthritis with the advent of biological agents, the mechanisms that drive cytokine production and sustain disease chronicity remain unknown. Tenascin-C (encoded by Tnc) is an extracellular matrix glycoprotein specifically expressed at areas of inflammation and tissue damage in inflamed rheumatoid joints. Here we show that mice that do not express tenascin-C show rapid resolution of acute joint inflammation and are protected from erosive arthritis. Intra-articular injection of tenascin-C promotes joint inflammation in vivo in mice, and addition of exogenous tenascin-C induces cytokine synthesis in explant cultures from inflamed synovia of individuals with rheumatoid arthritis. Moreover, in human macrophages and fibroblasts from synovia of individuals with rheumatoid arthritis, tenascin-C induces synthesis of proinflammatory cytokines via activation of Toll-like receptor 4 (TLR4). Thus, we have identified tenascin-C as a novel endogenous activator of TLR4-mediated immunity that mediates persistent synovial inflammation and tissue destruction in arthritic joint disease.
History
Publication status
- Published
Journal
Nature MedicineISSN
1078-8956Publisher
Nature Publishing GroupExternal DOI
Issue
7Volume
15Page range
774-80Department affiliated with
- Clinical and Experimental Medicine Publications
Notes
IDS Number: 468HEFull text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2011-08-22Usage metrics
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