Departments of Immunology and of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Physiol Rev. 2015 Jan;95(1):149-78. doi: 10.1152/physrev.00009.2014.
Nucleotide binding oligomerization domain (NOD)-like receptors are cytoplasmic pattern-recognition receptors that together with RIG-I-like receptor (retinoic acid-inducible gene 1), Toll-like receptor (TLR), and C-type lectin families make up the innate pathogen pattern recognition system. There are 22 members of NLRs in humans, 34 in mice, and even a larger number in some invertebrates like sea urchins, which contain more than 200 receptors. Although initially described to respond to intracellular pathogens, NLRs have been shown to play important roles in distinct biological processes ranging from regulation of antigen presentation, sensing metabolic changes in the cell, modulation of inflammation, embryo development, cell death, and differentiation of the adaptive immune response. The diversity among NLR receptors is derived from ligand specificity conferred by the leucine-rich repeats and an NH2-terminal effector domain that triggers the activation of different biological pathways. Here, we describe NLR genes associated with different biological processes and the molecular mechanisms underlying their function. Furthermore, we discuss mutations in NLR genes that have been associated with human diseases.
核苷酸结合寡聚化结构域 (NOD)-样受体是细胞内模式识别受体，与 RIG-I 样受体 (维甲酸诱导基因 1)、Toll 样受体 (TLR) 和 C 型凝集素家族一起构成先天病原体模式识别系统。人类有 22 种 NLR 成员，小鼠有 34 种，甚至一些无脊椎动物如海胆中也有更多的受体，包含超过 200 种受体。尽管最初被描述为对内源性病原体的反应，但 NLR 已被证明在从抗原呈递的调节、细胞内代谢变化的感知、炎症的调节、胚胎发育、细胞死亡和适应性免疫反应的分化等不同生物学过程中发挥重要作用。NLR 受体的多样性来源于富含亮氨酸重复序列和 NH2 末端效应结构域赋予的配体特异性，这些结构域触发不同生物学途径的激活。在这里，我们描述了与不同生物学过程相关的 NLR 基因以及它们功能的分子机制。此外，我们还讨论了与人类疾病相关的 NLR 基因突变。
