Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Faculty of Pharmacy, Department of Pharmaceutical Sciences and Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan.
Adv Exp Med Biol. 2024;1444:97-108. doi: 10.1007/978-981-99-9781-7_7.
Nucleic acid (NA)-sensing Toll-like receptors (TLRs) reside in the endosomal compartment of innate immune cells, such as macrophages and dendritic cells. NAs transported to the endosomal compartment are degraded by DNases and RNases. Degradation products, including single-stranded DNA, oligoRNA, and nucleosides, are recognized by TLR7, TLR8, and TLR9 to drive the defense responses against pathogens. NA degradation influences endosomal TLR responses by generating and degrading TLR ligands. TLR ligand accumulation because of impaired NA degradation causes constitutive TLR activation, leading to autoinflammatory and autoimmune diseases. Furthermore, some genes associated with these diseases promote endosomal TLR responses. Therefore, endosomal TLRs are promising therapeutic targets for TLR-mediated inflammatory diseases, and novel drugs targeting TLRs are being developed.
核酸（NA）感应 Toll 样受体（TLR）存在于先天免疫细胞（如巨噬细胞和树突状细胞）的内体区室中。被转运到内体区室的 NAs 被 DNase 和 RNase 降解。降解产物，包括单链 DNA、寡 RNA 和核苷，被 TLR7、TLR8 和 TLR9 识别，以驱动针对病原体的防御反应。NA 降解通过产生和降解 TLR 配体来影响内体 TLR 反应。由于 NA 降解受损导致 TLR 配体的积累，从而导致组成性 TLR 激活，导致自身炎症性和自身免疫性疾病。此外，一些与这些疾病相关的基因促进内体 TLR 反应。因此，内体 TLR 是 TLR 介导的炎症性疾病的有前途的治疗靶点，并且正在开发针对 TLR 的新型药物。
