Mechanistic perspectives on anti-aminoacyl-tRNA synthetase syndrome.
Mechanistic perspectives on anti-aminoacyl-tRNA synthetase syndrome.
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DOI：
10.1016/j.tibs.2022.09.011
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发表时间：
2022-10
影响因子：
13.8
通讯作者：
S. Kanaji;Wenqian Chen;Y. Morodomi;Ryan Shapiro;T. Kanaji;Xiang-Lei Yang
中科院分区：
文献类型：
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作者：
S. Kanaji;Wenqian Chen;Y. Morodomi;Ryan Shapiro;T. Kanaji;Xiang-Lei Yang
抗合成酶综合征（ASSD）是一种自身免疫性疾病，其特征是针对八种氨酰-tRNA合成酶（aaRS）之一的循环自身抗体。虽然这些自身抗体被认为在ASSD发病机制中起关键作用，但其作用的性质仍不清楚。在这里，我们描述ASSD的发病机制，并讨论ASSD连接aaRS-从WHEP域，可能赋予免疫原性的tRNA的作用，引发先天免疫反应和分泌的aaRS从细胞。通过这些探索，我们认为ASSD的发病机制涉及aaRS的组织特异性分泌，细胞外tRNA或tRNA片段及其参与Toll样受体信号传导的能力可能是重要的疾病因素。
Antisynthetase syndrome (ASSD) is an autoimmune disease characterized by circulating autoantibodies against one of eight aminoacyl-tRNA synthetases (aaRSs). Although these autoantibodies are believed to play critical roles in ASSD pathogenesis, the nature of their roles remains unclear. Here we describe ASSD pathogenesis and discuss ASSD-linked aaRSs – from the WHEP domain that may impart immunogenicity to the role of tRNA in eliciting the innate immune response and the secretion of aaRSs from cells. Through these explorations, we propose that ASSD pathogenesis involves the tissue-specific secretion of aaRSs and that extracellular tRNAs or tRNA fragments and their ability to engage Toll-like receptor signaling may be important disease factors.