New insights into the functional role of the rheumatoid arthritis shared epitope

被引：31
|
作者：
de Almeida, Denise E. [1 ]
Ling, Song [1 ]
Holoshitz, Joseph [1 ]
机构：
[1] Univ Michigan, Sch Med, Med Ctr, Dept Internal Med, Ann Arbor, MI 48109 USA
来源：
FEBS LETTERS | 2011年 / 585卷 / 23期
基金：
美国国家卫生研究院;
关键词：
Calreticulin; Nitric oxide; Oxidative stress; Rheumatoid arthritis; Shared epitope; Th17; NITRIC-OXIDE PRODUCTION; COLLAGEN-INDUCED ARTHRITIS; CELL-SURFACE CALRETICULIN; MAJOR HISTOCOMPATIBILITY COMPLEX; SYSTEMIC-LUPUS-ERYTHEMATOSUS; REGULATORY T-CELLS; DENDRITIC CELLS; INDOLEAMINE 2,3-DIOXYGENASE; OXIDATIVE-STRESS; RISK-FACTORS;
D O I：
10.1016/j.febslet.2011.03.035
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The shared epitope (SE) - an HLA-DRB1-encoded 5-amino acid sequence motif carried by the vast majority of rheumatoid arthritis (RA) patients - is a risk factor for severe disease. The mechanistic basis of RA-SE association is unknown. This group has previously demonstrated that the SE acts as a signal transduction ligand that activates nitric oxide and reactive oxygen species production. SE-activated signaling depends on cell surface calreticulin, a known innate immunity receptor previously implicated in immune regulation, autoimmunity and angiogenesis. Recent evidence that the SE enhances the polarization of Th17 cells, which is a key mechanism in autoimmunity, is discussed highlighting one of several potential functional effects of the SE in RA. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码：3619 / 3626
页数：8
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