TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity

被引：387
|
作者：
Baccala, Roberto [1 ]
Hoebe, Kasper [1 ]
Kono, Dwight H. [1 ]
Beutler, Bruce [1 ]
Theofilopoulos, Argyrios N. [1 ]
机构：
[1] Scripps Res Inst, Dept Immunol, La Jolla, CA 93037 USA
来源：
NATURE MEDICINE | 2007年 / 13卷 / 05期
关键词：
D O I：
10.1038/nm1590
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：
We formulate a two-phase paradigm of autoimmunity associated with systemic lupus erythematosus, the archetypal autoimmune disease. The initial Toll-like receptor (TLR)-independent phase is mediated by dendritic cell uptake of apoptotic cell debris and associated nucleic acids, whereas the subsequent TLR-dependent phase serves an amplification function and is mediated by uptake of TLR ligands derived from self-antigens (principally nucleic acids) complexed with autoantibodies. Both phases depend on elaboration of type I interferons (IFNs), and therapeutic interruption of induction or activity of these cytokines in predisposed individuals might have a substantial mitigating effect in lupus and other autoimmune diseases.
引用
收藏
页码：543 / 551
页数：9
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