Emerging significance of NLRs in inflammatory bowel disease.
Emerging significance of NLRs in inflammatory bowel disease.
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DOI：
10.1097/mib.0000000000000151
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发表时间：
2014-12
影响因子：
4.9
通讯作者：
Allen IC
中科院分区：
文献类型：
--
作者：
Davis BK;Philipson C;Hontecillas R;Eden K;Bassaganya-Riera J;Allen IC
模式识别受体是胃肠道系统中宿主防御和炎症的重要介质。最近的数据显示，Toll样受体和核苷酸结合区以及富含亮氨酸重复序列的蛋白(NLR)具有维持宿主微生物群和粘膜免疫之间的动态平衡的功能。NLR蛋白是一类不同的细胞质模式识别受体。在人类中，只有大约一半的已识别的NLR得到了充分的表征。大多数特征良好的NLR参与形成一个多蛋白复合体，称为炎症体，负责IL-1β和IL-18的成熟。然而，最近的观察也发现了一个新的NLR亚群的存在，它通过调节关键信号通路发挥炎症的积极或消极调节作用，包括核因子-κB。我们自己的初步回溯性数据挖掘工作已经确定了一系列不同的NLR，这些NLR在IBD患者结肠的信使RNA水平上发生了显着变化。同样，使用转基因小鼠品系的研究表明，多个NLR家族成员有可能在IBD期间显著调节免疫反应。靶向NLR信号转导是一种很有前途的新的治疗策略。然而，要将目前对NLR生物学的理解转化为有效的治疗方法，需要做出重大努力。
Pattern recognition receptors are essential mediators of host defense and inflammation in the gastrointestinal system. Recent data have revealed that toll-like receptors and nucleotide-binding domain and leucine-rich repeat-containing proteins (NLRs) function to maintain homeostasis between the host microbiome and mucosal immunity. The NLR proteins are a diverse class of cytoplasmic pattern recognition receptors. In humans, only about half of the identified NLRs have been adequately characterized. The majority of well-characterized NLRs participate in the formation of a multiprotein complex, termed the inflammasome, which is responsible for the maturation of interleukin-1β and interleukin-18. However, recent observations have also uncovered the presence of a novel subgroup of NLRs that function as positive or negative regulators of inflammation through modulating critical signaling pathways, including NF-κB. Dysregulation of specific NLRs from both proinflammatory and inhibitory subgroups have been associated with the development of inflammatory bowel disease (IBD) in genetically susceptible human populations. Our own preliminary retrospective data mining efforts have identified a diverse range of NLRs that are significantly altered at the messenger RNA level in colons from patients with IBD. Likewise, studies using genetically modified mouse strains have revealed that multiple NLR family members have the potential to dramatically modulate the immune response during IBD. Targeting NLR signaling represents a promising and novel therapeutic strategy. However, significant effort is necessary to translate the current understanding of NLR biology into effective therapies.