Mechanistic perspectives on anti-aminoacyl-tRNA synthetase syndrome.

Sachiko Kanaji, Wenqian Chen, Yosuke Morodomi, Ryan Shapiro, Taisuke Kanaji, Xiang-Lei Yang

Trends in biochemical sciences 2023 Mar

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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. Copyright © 2022 Elsevier Ltd. All rights reserved.

Citation

Sachiko Kanaji, Wenqian Chen, Yosuke Morodomi, Ryan Shapiro, Taisuke Kanaji, Xiang-Lei Yang. Mechanistic perspectives on anti-aminoacyl-tRNA synthetase syndrome. Trends in biochemical sciences. 2023 Mar;48(3):288-302