Type I IFN system in the development and manifestations of SLE

被引:137
|
作者
Elkon, Keith B. [1 ]
Wiedeman, Alice
机构
[1] Univ Washington, Div Rheumatol, Seattle, WA 98195 USA
基金
美国国家卫生研究院;
关键词
nucleic acid sensor; systemic lupus erythematosus; type I interferon; PLASMACYTOID DENDRITIC CELLS; AICARDI-GOUTIERES-SYNDROME; INTERFERON-ALPHA PRODUCTION; LUPUS-ERYTHEMATOSUS; DISEASE-ACTIVITY; IMMUNE-COMPLEXES; EXPRESSION SIGNATURE; AUTOIMMUNE-DISEASE; C1Q DEFICIENCY; GENE SIGNATURE;
D O I
10.1097/BOR.0b013e3283562c3e
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Purpose of review Type I interferon (IFN-I) is strongly implicated in the pathogenesis of systemic lupus erythematosus (SLE). Here, we focus on new developments in pathways of IFN-I stimulation, the role of IFN-I in syndromes associated with lupus-like diseases, the utility of IFN-I signatures as biomarkers, and the progress of therapeutic agents targeting IFN-I pathways in SLE. Recent findings Immune complexesimmune complex are a dominant driver of IFN-I production by activating toll-like receptors (TLRs) in plasmacytoid dendritic cells (pDC) in SLE. The level of IFN-I production is attenuated by C1q in immune complexes and enhanced by natural killer (NK) cells as well as by activated platelets that express CD40L. In addition to immune complexs, cell-intrinsic activation pathways utilize recently described non-TLR RNA and DNA sensors. Some modules or clusters of IFN-I stimulated genes or proteins correlate with disease activity, whereas IFN-I biomarkers of disease flare or specific clinical manifestations need further study. IFN-I blocking studies have reached phase II clinical trials. Summary Significant progress has been made in defining both TLR as well as non-TLR mediated stimulation of IFN-I. This has helped elucidate the mechanisms of several mutations and common genetic variations in predisposing to SLE. Challenges remain in the establishing the utility of biomarkers and the role of IFN-I blockade in the clinical management of patients with this disease.
引用
收藏
页码:499 / 505
页数:7
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