Voss Timo-Daniel, Hezinger Lucy, Kufer Thomas A
University of Hohenheim, Institute for Nutritional Medicine, Department of Immunology, Stuttgart, Germany.
Adv Exp Med Biol. 2025;1476:83-105. doi: 10.1007/978-3-031-85340-1_4.
Nucleotide-binding oligomerization domain-like receptors (NLRs) are a family of cytosolic pattern recognition receptors (PRRs) and able to respond to conserved microbe-associated molecular patterns (MAMPs) and endogenous damage-associated molecular patterns (DAMPs). NLRs modulate the inflammatory response via multiple pathways including nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB)-activation, mitogen-activated protein kinase (MAPK)-pathways and both canonical and non-canonical inflammasome formation. The latter results in auto-processing of caspase-1 and subsequent maturation of the cytokines interleukin 1 beta (IL-1β) and IL-18 as well as induction of pyroptosis by cleavage of gasdermin D (GSDMD) that induces pores in the cell membrane. NLRs act in synergy with other PRRs but some NLRs directly modulate adaptive immunity via transcriptional regulation of major histocompatibility complex (MHC) class I and class II. NLRs have an essential role as intracellular PRRs and thereby orchestrate inflammatory responses. NLR mutations and subsequent dysfunction can result in cancer or autoinflammatory diseases, such as Crohn's disease and ulcerative colitis, and many more, indicating their important role in classical immune recognition, maintenance of tissue homeostasis and reproductive functions. Here, we discuss our current understanding of mammalian NLRs that act as PRRs.
核苷酸结合寡聚化结构域样受体（NLRs）是一类胞质模式识别受体（PRRs），能够对保守的微生物相关分子模式（MAMPs）和内源性损伤相关分子模式（DAMPs）作出反应。NLRs通过多种途径调节炎症反应，包括激活B细胞的核因子κB轻链增强子（NF-κB）、丝裂原活化蛋白激酶（MAPK）途径以及经典和非经典炎性小体的形成。后者导致半胱天冬酶-1的自加工以及细胞因子白细胞介素1β（IL-1β）和IL-18的随后成熟，以及通过切割在细胞膜上诱导孔道的gasdermin D（GSDMD）来诱导细胞焦亡。NLRs与其他PRRs协同作用，但一些NLRs通过对主要组织相容性复合体（MHC）I类和II类的转录调控直接调节适应性免疫。NLRs作为细胞内PRRs发挥着重要作用，从而协调炎症反应。NLR突变及随后的功能障碍可导致癌症或自身炎症性疾病，如克罗恩病和溃疡性结肠炎等多种疾病，这表明它们在经典免疫识别、组织稳态维持和生殖功能中发挥着重要作用。在此，我们讨论目前对作为PRRs的哺乳动物NLRs的理解。
