Institute of Nutritional Medicine, University of Hohenheim, 70593 Stuttgart, Germany; and.
Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50931 Cologne, Germany.
J Immunol. 2019 Jan 1;202(1):218-227. doi: 10.4049/jimmunol.1800334. Epub 2018 Dec 3.
NOD-like receptors (NLR) are critical regulators of innate immune signaling. The NLR family consists of 22 human proteins with a conserved structure containing a central oligomerization NACHT domain, an N-terminal interaction domain, and a variable number of C-terminal leucine-rich repeats. Most NLR proteins function as cytosolic pattern recognition receptors with activation of downstream inflammasome signaling, NF-κB, or MAPK activation. Although NLRP10 is the only NLR protein lacking the leucine rich repeats, it has been implicated in multiple immune pathways, including the regulation of inflammatory responses toward and infection. In this study, we identify Abin-1, a negative regulator of NF-κB, as an interaction partner of NLRP10 that binds to the NACHT domain of NLRP10. Using as an infection model in human epithelial cells, our work reveals a novel function of NLRP10 in destabilizing Abin-1, resulting in enhanced proinflammatory signaling. Our data give insight into the molecular mechanism underlying the function of NLRP10 in innate immune responses.
核苷酸结合寡聚化结构域样受体（NOD-like receptors，NLRs）是先天免疫信号的关键调节因子。NLR 家族由 22 种人类蛋白组成，具有保守的结构，包含一个中央寡聚化 NACHT 结构域、一个 N 端相互作用结构域和可变数量的 C 端亮氨酸富含重复序列。大多数 NLR 蛋白作为细胞溶质模式识别受体发挥作用，激活下游炎症小体信号、NF-κB 或 MAPK 激活。尽管 NLRP10 是唯一缺乏亮氨酸丰富重复序列的 NLR 蛋白，但它已被涉及多种免疫途径，包括对 和 感染的炎症反应的调节。在这项研究中，我们确定了 Abin-1，一种 NF-κB 的负调节剂，作为 NLRP10 的相互作用伙伴，与 NLRP10 的 NACHT 结构域结合。使用 作为人类上皮细胞中的感染模型，我们的工作揭示了 NLRP10 在不稳定 Abin-1 中增强促炎信号的新功能。我们的数据深入了解了 NLRP10 在先天免疫反应中的功能的分子机制。
