作为自身免疫性疾病治疗靶点的内体 Toll-Like 受体

4区医学 Q2 Biochemistry, Genetics and Molecular Biology

Advances in experimental medicine and biology Pub Date : 2024-01-01 DOI:10.1007/978-981-99-9781-7_7

Kensuke Miyake, Takuma Shibata, Ryutaro Fukui, Yusuke Murakami, Ryota Sato, Ryosuke Hiranuma

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引用次数: 0

摘要

核酸（NA）感应的 Toll 样受体（TLRs）存在于巨噬细胞和树突状细胞等先天性免疫细胞的内体腔室中。被转运到内泌体区室的 NA 会被 DNase 和 RNases 降解。降解产物（包括单链 DNA、寡核糖核酸和核苷）会被 TLR7、TLR8 和 TLR9 识别，从而驱动针对病原体的防御反应。NA 降解通过生成和降解 TLR 配体影响内体 TLR 反应。由于 NA 降解受损，TLR 配体积聚，导致 TLR 激活，从而引发自身炎症和自身免疫性疾病。此外，与这些疾病相关的一些基因会促进内体 TLR 反应。因此，内体 TLR 是治疗 TLR 介导的炎症性疾病的有希望的治疗靶点，目前正在开发以 TLR 为靶点的新型药物。

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Endosomal Toll-Like Receptors as Therapeutic Targets for Autoimmune Diseases.

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.

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来源期刊

Advances in experimental medicine and biology 医学-医学：研究与实验

CiteScore

5.90

自引率

0.00%

发文量

465

审稿时长

2-4 weeks

期刊介绍： Advances in Experimental Medicine and Biology provides a platform for scientific contributions in the main disciplines of the biomedicine and the life sciences. This series publishes thematic volumes on contemporary research in the areas of microbiology, immunology, neurosciences, biochemistry, biomedical engineering, genetics, physiology, and cancer research. Covering emerging topics and techniques in basic and clinical science, it brings together clinicians and researchers from various fields.