自身免疫性疾病是以免疫系统失调为特征的慢性免疫性疾病,最终导致自身抗原耐受性的破坏。累积数据表明,核苷酸结合和寡聚化结构域(NOD)样受体(NLR)在各种自身免疫性疾病中发挥重要作用,如炎症性肠病(IBD),类风湿性关节炎(RA),系统性红斑狼疮(SLE),牛皮癣,多发性硬化症(MS),等。NLR蛋白,由C端富含亮氨酸的重复序列(LRR)组成,一个中央核苷酸结合域,和一个N末端效应子结构域,形成一组模式识别受体(PRR),通过特异性识别细胞病原体相关分子模式(PAMP)或损伤相关分子模式(DAMP)并触发许多信号通路来介导免疫反应,包括RIP2激酶,caspase-1,核因子κB(NF-κB),丝裂原活化蛋白激酶(MAPK)等。基于它们的N端域,NLR分为五个亚家族:NLRA,NLRB,NLRC,NLRP,和NLRX1。在这次审查中,我们简要描述了NLRs的结构和信号通路,NLR信号通路在自身免疫性疾病发生发展中的研究进展,以及强调许多天然产物和合成化合物靶向NLRs用于治疗自身免疫性疾病。
Autoimmune diseases are chronic immune diseases characterized by dysregulation of immune system, which ultimately results in a disruption in self-antigen tolerance. Cumulative data show that nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) play essential roles in various autoimmune diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis, multiple sclerosis (MS), etc. NLR proteins, consisting of a C-terminal leucine-rich repeat (LRR), a central nucleotide-binding domain, and an N-terminal effector domain, form a group of pattern recognition receptors (PRRs) that mediate the immune response by specifically recognizing cellular pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) and triggering numerous signaling pathways, including RIP2 kinase, caspase-1, nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK) and so on. Based on their N-terminal domain, NLRs are divided into five subfamilies: NLRA, NLRB, NLRC, NLRP, and NLRX1. In this review, we briefly describe the structures and signaling pathways of NLRs, summarize the recent progress on NLR signaling in the occurrence and development of autoimmune diseases, as well as highlight numerous natural products and synthetic compounds targeting NLRs for the treatment of autoimmune diseases.