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模式识别受体在健康与疾病中的作用

Pattern recognition receptors in health and diseases.

机构信息

Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan, China.

The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.

出版信息

Signal Transduct Target Ther. 2021 Aug 4;6(1):291. doi: 10.1038/s41392-021-00687-0.

Abstract

Pattern recognition receptors (PRRs) are a class of receptors that can directly recognize the specific molecular structures on the surface of pathogens, apoptotic host cells, and damaged senescent cells. PRRs bridge nonspecific immunity and specific immunity. Through the recognition and binding of ligands, PRRs can produce nonspecific anti-infection, antitumor, and other immunoprotective effects. Most PRRs in the innate immune system of vertebrates can be classified into the following five types based on protein domain homology: Toll-like receptors (TLRs), nucleotide oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), C-type lectin receptors (CLRs), and absent in melanoma-2 (AIM2)-like receptors (ALRs). PRRs are basically composed of ligand recognition domains, intermediate domains, and effector domains. PRRs recognize and bind their respective ligands and recruit adaptor molecules with the same structure through their effector domains, initiating downstream signaling pathways to exert effects. In recent years, the increased researches on the recognition and binding of PRRs and their ligands have greatly promoted the understanding of different PRRs signaling pathways and provided ideas for the treatment of immune-related diseases and even tumors. This review describes in detail the history, the structural characteristics, ligand recognition mechanism, the signaling pathway, the related disease, new drugs in clinical trials and clinical therapy of different types of PRRs, and discusses the significance of the research on pattern recognition mechanism for the treatment of PRR-related diseases.

摘要

模式识别受体(PRRs)是一类能够直接识别病原体、凋亡宿主细胞和衰老损伤细胞表面特定分子结构的受体。PRRs 桥接非特异性免疫和特异性免疫。通过配体的识别和结合,PRRs 可以产生非特异性抗感染、抗肿瘤和其他免疫保护作用。脊椎动物固有免疫系统中的大多数 PRRs 可以根据蛋白结构域同源性分为以下五种类型:Toll 样受体(TLRs)、核苷酸寡聚化结构域(NOD)样受体(NLRs)、维甲酸诱导基因-I(RIG-I)样受体(RLRs)、C 型凝集素受体(CLRs)和黑色素瘤缺失 2(AIM2)样受体(ALRs)。PRRs 基本由配体识别结构域、中间结构域和效应结构域组成。PRRs 通过其效应结构域识别和结合各自的配体,并募集具有相同结构的衔接分子,启动下游信号通路发挥作用。近年来,对 PRRs 及其配体的识别和结合的研究不断深入,极大地促进了对不同 PRRs 信号通路的理解,并为免疫相关疾病甚至肿瘤的治疗提供了思路。本文详细描述了不同类型 PRRs 的历史、结构特征、配体识别机制、信号通路、相关疾病、临床试验中的新药以及临床治疗,讨论了研究模式识别机制在治疗 PRR 相关疾病中的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67d2/8333067/10f8968da651/41392_2021_687_Fig1_HTML.jpg

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