Abstract：
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.
摘要：
核酸（NA）敏感的Toll样受体（TLR）驻留在先天免疫细胞的内体区室，如巨噬细胞和树突状细胞。转运到内体区室的NA被DNA酶和RNA酶降解。降解产品,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配体影响内体TLR应答。由于受损的NA降解导致TLR配体积累，导致自身炎症和自身免疫性疾病。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TLRs是TLR介导的炎性疾病的有希望的治疗靶点，和靶向TLRs的新型药物正在开发中。
