Long interspersed nuclear elements (LINE-1): Potential triggers of systemic autoimmune disease
Long interspersed nuclear elements (LINE-1): Potential triggers of systemic autoimmune disease
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DOI：
10.3109/08916930903374865
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发表时间：
2010-02-01
期刊：
影响因子：
3.5
通讯作者：
Crow, Mary K.
中科院分区：
文献类型：
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作者：
Crow, Mary K.
最近的进展已经鉴定了含有核酸的免疫复合物作为Toll样受体的刺激物和I型干扰素（IFN）的诱导物。虽然在系统性自身免疫性疾病的背景下，类似的机制可能有助于放大体内免疫系统的激活和炎症介质的产生，但自身免疫的最初触发因素尚未确定。在这篇综述中，我们描述了一类潜在的自身免疫诱导剂，内源性retorelements，特别关注长散置核元素（LINE-1，L1）。L1转录物的表达增加或L1 DNA或RNA的降解减少可以为先天性免疫应答、免疫系统的引发以及自身免疫和炎症的诱导提供有效的刺激。个体间的基因组和遗传变异、L1调控中的性别相关差异以及环境触发因素是可能导致L1表达增加的潜在机制。通过TLR非依赖性途径由富含L1的核酸诱导I型IFN可能代表导致系统性自身免疫性疾病的复杂系列事件的第一步。
Recent advances have identified immune complexes containing nucleic acids as stimuli for toll-like receptors and inducers of type I interferon (IFN). While a similar mechanism may serve to amplify immune system activation and production of inflammatory mediators in vivo in the context of systemic autoimmune diseases, the initial triggers of autoimmunity have not been defined. In this review, we describe a category of potential inducers of autoimmunity, the endogenous retroelements, with a particular focus on long interspersed nuclear elements (LINE-1, L1). Increased expression of L1 transcripts or decreased degradation of L1 DNA or RNA could provide potent stimuli for an innate immune response, priming of the immune system, and induction of autoimmunity and inflammation. Genomic and genetic variations among individuals, sex-related differences in L1 regulation, and environmental triggers are among the potential mechanisms that might account for increased L1 expression. Induction of type I IFN by L1-enriched nucleic acids through TLR-independent pathways could represent a first step in the complex series of events leading to systemic autoimmune disease.