The Ro60 autoantigen binds endogenous retroelements and regulates inflammatory gene expression.
The Ro60 autoantigen binds endogenous retroelements and regulates inflammatory gene expression.
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DOI：
10.1126/science.aac7442
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发表时间：
2015-10-23
期刊：
影响因子：
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通讯作者：
Behrens TW
中科院分区：
文献类型：
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作者：
Hung T;Pratt GA;Sundararaman B;Townsend MJ;Chaivorapol C;Bhangale T;Graham RR;Ortmann W;Criswell LA;Yeo GW;Behrens TW
在系统性红斑狼疮(SLE)和干燥综合征中，自身抗体针对RNA结合蛋白Ro60。然而，Ro60及其相关RNA是否参与疾病的发病机制尚不清楚。我们对人类细胞系中与Ro60相关的RNA进行了编目，发现在其他RNA中，Ro60结合了来自内源性Alu逆转录元件的RNA基序。ALU转录本由I型干扰素诱导，并刺激人外周血细胞分泌促炎细胞因子。Ro60缺失导致Alu RNA和干扰素调节基因表达增强。抗Ro60阳性的SLE免疫复合物含有Alu RNA，与对照组相比，Alu转录本在SLE全血样本中上调。这些发现建立了狼疮自身抗原Ro60、Alu逆转录元件和I型干扰素之间的联系。
Autoantibodies target the RNA binding protein Ro60 in systemic lupus erythematosus (SLE) and Sjögren’s syndrome. However, whether Ro60 and its associated RNAs contribute to disease pathogenesis is unclear. We catalogued the Ro60-associated RNAs in human cell lines and found that among other RNAs, Ro60 bound an RNA motif derived from endogenous Alu retroelements. Alu transcripts were induced by type I interferon and stimulated proinflammatory cytokine secretion by human peripheral blood cells. Ro60 deletion resulted in enhanced expression of Alu RNAs and interferon-regulated genes. Anti-Ro60 positive SLE immune complexes contained Alu RNAs, and Alu transcripts were upregulated in SLE whole blood samples compared to controls. These findings establish a link between the lupus autoantigen Ro60, Alu retroelements and type I interferon.