Endosomal Toll-like receptors in clinically overt and silent autoimmunity.
Endosomal Toll-like receptors in clinically overt and silent autoimmunity.
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DOI：
10.1111/imr.12383
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发表时间：
2016-01
影响因子：
8.7
通讯作者：
Buyon JP
中科院分区：
文献类型：
--
作者：
Clancy RM;Markham AJ;Buyon JP
Toll样受体（TLR）最初被鉴定为模式识别受体，现在被认为是先天免疫和适应性免疫之间的关键界面。系统性红斑狼疮（SLE）的特征在于由凋亡或坏死细胞释放的内源性核酸对先天性和适应性免疫系统的连续和循环刺激。TLR 7和TLR 9作为病毒感染的先天传感器发挥作用，因为它们的配体分别是ssRNA和dsDNA。B细胞和pDC中的内体TLR对自身核酸的识别被认为是SLE发病机制中的重要步骤，产生抗核抗体并产生I型IFN。在这篇综述中，我们具体看看TLR 7，非编码RNA和SSA/Ro 60如何有助于新生儿狼疮（NL）背景下的临床自身免疫和器官损伤。尽管NL的发病率比SLE低15倍，但它提供了一个独特的机会来研究自身免疫的两个不同方面：发育中胎儿的被动获得性组织损伤和无症状母亲的疾病临床进展，仅在发现心脏传导阻滞后才发现抗Ro 60自身抗体/皮疹儿童。最后，我们讨论了无症状受试者使用羟氯喹（HCQ）可能会阻止自身免疫的临床表现。
Toll-like receptors (TLRs), first identified as pattern recognition receptors, are now recognized to serve as a key interface between innate and adaptive immunity. Systemic Lupus Erythematosus (SLE) is characterized by both continuous and cyclic stimulation of the innate and adaptive immune system by endogenous nucleic acids released from apoptotic or necrotic cells. TLR7 and TLR9 function as innate sensors of viral infection as their ligands are ssRNA and dsDNA, respectively. Recognition of self nucleic acids by endosomal TLRs in B cells and pDCs is thought to be an important step in the pathogenesis of SLE, generating anti-nuclear antibodies and producing type I IFN. In this review, we take a specific look at how TLR7, noncoding RNA, and SSA/Ro60 can contribute to clinical autoimmunity and organ damage in the context of neonatal lupus (NL). Although fifteen times less common than SLE, NL provides a unique opportunity to study two different aspects of autoimmunity: passively acquired tissue injury in a developing fetus and clinical progression of disease in an asymptomatic mother found to have anti-Ro60 autoantibodies only after identification of heart block/rash in a child. Finally, we discuss hydroxychloroquine (HCQ) use by asymptomatic subjects which may forestall the clinical expression of autoimmunity.