Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Trends Biochem Sci. 2023 Mar;48(3):288-302. doi: 10.1016/j.tibs.2022.09.011. Epub 2022 Oct 21.
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.
抗合成酶综合征（ASSD）是一种自身免疫性疾病，其特征是循环中有针对八种氨酰-tRNA 合成酶（aaRSs）之一的自身抗体。尽管这些自身抗体被认为在 ASSD 的发病机制中起关键作用，但它们的作用性质尚不清楚。在这里，我们描述了 ASSD 的发病机制，并讨论了 ASSD 相关的 aaRSs - 从可能赋予免疫原性的 WHEP 结构域到 tRNA 在引发先天免疫反应和 aaRSs 从细胞中分泌的作用。通过这些探索，我们提出 ASSD 的发病机制涉及 aaRSs 的组织特异性分泌，细胞外 tRNA 或 tRNA 片段及其与 Toll 样受体信号的相互作用可能是重要的疾病因素。
