State Key Laboratory of Freshwater Ecology and Biotechnology, Key Laboratory of Aquaculture Disease Control, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, China; Innovation Academy for Seed Design, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.
State Key Laboratory of Freshwater Ecology and Biotechnology, Key Laboratory of Aquaculture Disease Control, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, China.
Dev Comp Immunol. 2021 Jan;114:103859. doi: 10.1016/j.dci.2020.103859. Epub 2020 Sep 5.
The nucleotide-binding domain and leucine-rich repeat-containing family (NLR) proteins are innate immune sensors which recognize highly conserved pathogen-associated molecular patterns (PAMPs). Mammals have small numbers of NLR proteins, whereas in some species such as in invertebrates and jawless vertebrates, NLRs have expanded into very large families. Nearly 400 NLR proteins are identified in the zebrafish genome. Members of the NLR family can be divided into two functional sub-groups based on their ability to either positively or negatively regulate host immune response or inflammatory signaling cascades. Mammalian NLRC3 has been identified as an inhibitory NLR, and serves as a negative regulator in the NF-κB-mediated inflammatory response, STING-mediated DNA sensing and PI3K-mTOR pathways. Different from mammalian NLRC3, the analysis from genomes or transcriptomes revealed that the expansions of NLRC3 existed in different species of fish. Furthermore, piscine NLRC3-like genes were confirmed to have a negative or positive regulatory function in response to different kinds of pathogen infections and in the production of proinflammatory cytokines. In this review, we summarize recent advances in our understanding of the expanding and function of NLRC3 or NLRC3-like genes in teleost fish, and give our view of important directions for future studies. The knowledge of piscine NLRC3 or expansive NLRC3-like genes-mediated biological functions in homeostasis and diseases will shed new light on the prevention and control of inflammatory and/or infectious diseases.
核苷酸结合域和富含亮氨酸重复序列家族（NLR）蛋白是先天免疫传感器，可识别高度保守的病原体相关分子模式（PAMPs）。哺乳动物的 NLR 蛋白数量较少，而在某些物种（如无脊椎动物和无颌脊椎动物）中，NLR 已扩展成非常大的家族。在斑马鱼基因组中鉴定出近 400 种 NLR 蛋白。根据其是否能够积极或消极调节宿主免疫反应或炎症信号级联的能力，NLR 家族成员可分为两个功能亚群。哺乳动物 NLRC3 被鉴定为抑制性 NLR，作为 NF-κB 介导的炎症反应、STING 介导的 DNA 感应和 PI3K-mTOR 途径中的负调节剂。与哺乳动物 NLRC3 不同，对基因组或转录组的分析表明，NLRC3 的扩张存在于不同鱼类物种中。此外，鱼类 NLRC3 样基因被证实具有负或正调节功能，以响应不同类型的病原体感染和促炎细胞因子的产生。在这篇综述中，我们总结了我们对硬骨鱼类 NLRC3 或 NLRC3 样基因扩张和功能的理解的最新进展，并对未来研究的重要方向提出了看法。对鱼类 NLRC3 或扩展的 NLRC3 样基因介导的内稳态和疾病中的生物学功能的了解将为炎症和/或传染性疾病的预防和控制提供新的思路。
