Department of Pathology, Academic Medical Center, Meibergdreef 9, L2-111, 1105 AZ Amsterdam, Netherlands.
Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ziemssenstraße 1, 80336 München, Germany.
Nat Rev Nephrol. 2014 Jul;10(7):398-414. doi: 10.1038/nrneph.2014.91. Epub 2014 Jun 3.
Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain receptors (NLRs) are families of pattern recognition receptors that, together with inflammasomes, sense and respond to highly conserved pathogen motifs and endogenous molecules released upon cell damage or stress. Evidence suggests that TLRs, NLRs and the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome have important roles in kidney diseases through regulation of inflammatory and tissue-repair responses to infection and injury. In this Review, we discuss the pathological mechanisms that are related to TLRs, NLRs and NLRP3 in various kidney diseases. In general, these receptors are protective in the host defence against urinary tract infection, but can sustain and self-perpetuate tissue damage in sterile inflammatory and immune-mediated kidney diseases. TLRs, NLRs and NLRP3, therefore, have become promising drug targets to enable specific modulation of kidney inflammation and suppression of immunopathology in kidney disease.
Toll 样受体 (TLRs) 和核苷酸结合寡聚化结构域受体 (NLRs) 是模式识别受体家族，它们与炎症小体一起，感知和响应高度保守的病原体基序和细胞损伤或应激时释放的内源性分子。有证据表明，TLRs、NLRs 和 NACHT、LRR 和 PYD 结构域包含蛋白 3 (NLRP3) 炎症小体通过调节对感染和损伤的炎症和组织修复反应，在肾脏疾病中发挥重要作用。在这篇综述中，我们讨论了与各种肾脏疾病中 TLRs、NLRs 和 NLRP3 相关的病理机制。一般来说，这些受体在宿主防御尿路感染中具有保护作用，但在无菌性炎症和免疫介导的肾脏疾病中，它们可以维持和自我延续组织损伤。因此，TLRs、NLRs 和 NLRP3 已成为有前途的药物靶点，能够特异性调节肾脏炎症和抑制肾脏疾病中的免疫病理。
