Allen Irving Coy
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University , Blacksburg, VA , USA.
Front Immunol. 2014 Apr 22;5:169. doi: 10.3389/fimmu.2014.00169. eCollection 2014.
Aberrant inflammation is an enabling characteristic of tumorigenesis. Thus, signaling cascades that alter inflammatory activation and resolution are of specific relevance to disease pathogenesis. Pattern recognition receptors (PRRs) are essential mediators of the host immune response and have emerged as critical elements affecting multiple facets of tumor pathobiology. The nucleotide-binding domain and leucine-rich repeat containing (NLR) proteins are intracellular PRRs that sense microbial and non-microbial products. Members of the NLR family can be divided into functional sub-groups based on their ability to either positively or negatively regulate the host immune response. Recent studies have identified a novel sub-group of non-inflammasome forming NLRs that negatively regulate diverse biological pathways associated with both inflammation and tumorigenesis. Understanding the mechanisms underlying the function of these unique NLRs will assist in the rationale design of future therapeutic strategies targeting a wide spectrum of inflammatory diseases and cancer. Here, we will discuss recent findings associated with this novel NLR sub-group and mechanisms by which these PRRs may function to alter cancer pathogenesis.
异常炎症是肿瘤发生的一个促成特征。因此,改变炎症激活和消退的信号级联与疾病发病机制具有特定相关性。模式识别受体(PRR)是宿主免疫反应的重要介质,并已成为影响肿瘤病理生物学多个方面的关键因素。含核苷酸结合域和富含亮氨酸重复序列(NLR)的蛋白是感知微生物和非微生物产物的细胞内PRR。NLR家族成员可根据其对宿主免疫反应进行正向或负向调节的能力分为功能亚组。最近的研究发现了一个新的非炎性小体形成NLR亚组,该亚组对与炎症和肿瘤发生相关的多种生物学途径具有负向调节作用。了解这些独特NLR功能的潜在机制将有助于合理设计未来针对广泛炎症性疾病和癌症的治疗策略。在此,我们将讨论与这个新的NLR亚组相关的最新发现以及这些PRR可能改变癌症发病机制的作用机制。