論文

査読有り
2011年3月

Anti-arthritic effect of E3 ubiquitin ligase, c-MIR, expression in the joints

INTERNATIONAL IMMUNOLOGY
  • Masayasu Toyomoto
  • ,
  • Satoshi Ishido
  • ,
  • Nobuyuki Miyasaka
  • ,
  • Hachiro Sugimoto
  • ,
  • Hitoshi Kohsaka

23
3
開始ページ
177
終了ページ
183
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1093/intimm/dxq470
出版者・発行元
OXFORD UNIV PRESS

Cellular modulator of immune recognition (c-MIR) is an E3 ubiquitin ligase that ubiquitinates MHC class II and CD86 for their endocytosis and subsequent lysosomal degradation. In accordance with their importance in antigen presentation, systemic c-MIR over-expression downmodulates adaptive immune responses. Rheumatoid arthritis (RA) is a chronic synovitis driven by autoimmunity in the joints. Since antigen-presenting cells, such as macrophages, dendritic cells (DCs) and rheumatoid factor-positive B cells are abundant in the rheumatoid synovial tissues, autoantigens released by tissue damage should be presented locally, leading to amplification of systemic arthritogenic immune responses. Assuming that inhibition of the antigen presentation in the synovial tissues should suppress systemic arthritis, we transferred the c-MIR gene to the hind leg synovial tissues from mice with type II collagen (CII)-induced arthritis, an animal model of RA. The gene was transferred adenovirally because adenoviruses can infect DC and macrophages in vivo. Unexpectedly, therapeutic effect was observed only in the treated joints. Splenocyte responses and serum antibodies against CII were not suppressed. Moreover, in vitro studies disclosed that c-MIR gene transfer suppressed IL-6 production from synovial fibroblasts stimulated with tumor necrosis factor (TNF)-alpha or IL-1 beta. Bone marrow-derived macrophages and DC from c-MIR transgenic mice were impaired in IL-6 and TNF-alpha production when stimulated with LPS. This suppression was controlled at the post-transcriptional level since their mRNA was not affected. These results have disclosed a new function of c-MIR, inhibition of inflammatory cytokine production. Induction of c-MIR in the joints could be a new therapeutic approach to the treatment of RA.

Web of Science ® 被引用回数 : 5

リンク情報
DOI
https://doi.org/10.1093/intimm/dxq470
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000288250000003&DestApp=WOS_CPL
ID情報
  • DOI : 10.1093/intimm/dxq470
  • ISSN : 0953-8178
  • Web of Science ID : WOS:000288250000003

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