期刊
NATURE MEDICINE
卷 15, 期 7, 页码 774-U11出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.1987
关键词
-
资金
- Arthritis Research Campaign
- The Kennedy Institute of Rheumatology Trustees
- UK Medical Research Council New Investigators Research Grant
- UK National Institute for Health Research Biomedical Research Centre
- Institut National du Cancer-Institut National de la Sante et de la Recherche Medicale
- Contrat d'interface with the Hospital Hautepierre
- MRC [G0700108] Funding Source: UKRI
- Medical Research Council [G0700108] Funding Source: researchfish
Although 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据