Immunology Catalyst, Immunology Network, Adaptive Immunity Research Unit, GlaxoSmithKline, Stevenage, UK.
School of Medicine, Institute of Infection and Immunity, University Hospital of Wales, Cardiff University, Cardiff, UK.
Immunology. 2021 Mar;162(3):249-251. doi: 10.1111/imm.13309.
Inflammasomes are generally thought of as large protein complexes that assemble in the cytosol in response to danger such as tissue damage or infection; once activated, they trigger production of inflammatory cytokines and drive cells towards a pro-inflammatory death - termed pyroptosis. Inflammasome activation is a two-step process; priming or Signal 1 (typically via Toll or other receptors that activate NF-kB) induces transcription of pro-forms of IL-1β and IL-18, while activation or Signal 2 (by many effectors, including a number of bacterial toxins that form pores in cell membranes) comprises activation of caspase-1 in the inflammasome that in turn cleaves pro-IL-1β and pro-IL-18 and induces release of the active pro-inflammatory cytokines. The most studied inflammasome is the NLRP3 inflammasome, but in addition to NLRP3, there are several lesser-known or enigmatic inflammasomes whose functions seem to range from non-canonical inflammasome activation, pathogen/damage, suppression or modulation of inflammation and even embryonic development. In this review series, which will be presented in two parts, we will focus on lesser-known inflammasomes, such as NLRP6 (non-canonical inflammasome activation), NLRP9 (restricting rotavirus infection in intestinal epithelial cells), NLRX1 (negative regulators of inflammation), NLRC5 (regulating antigen presentation) and NLRP7 (sensing of bacterial lipoproteins). Although the function of NLRP3 is understood, the functions of these lesser-studied inflammasomes are largely unstudied. Given that after a decade of research, new inflammasome and new inflammasome activators are still being discovered indicates that there is a lot more that we need to find out in the NLR field. Only by understanding all of the members of the NLR family, will we be able to target them therapeutically in the future.
炎症小体通常被认为是一种大型蛋白复合物，在细胞质中组装以响应组织损伤或感染等危险；一旦被激活，它们会触发炎症细胞因子的产生，并促使细胞向促炎死亡 - 称为细胞焦亡。炎症小体的激活是一个两步过程；启动或信号 1（通常通过 Toll 或其他激活 NF-κB 的受体）诱导 IL-1β 和 IL-18 的前体转录，而激活或信号 2（通过许多效应物，包括许多在细胞膜中形成孔的细菌毒素）包括炎症小体中 caspase-1 的激活，反过来又切割 pro-IL-1β 和 pro-IL-18，并诱导活性促炎细胞因子的释放。研究最多的炎症小体是 NLRP3 炎症小体，但除了 NLRP3 之外，还有几个鲜为人知或神秘的炎症小体，其功能似乎从非经典炎症小体激活、病原体/损伤、炎症的抑制或调节，甚至胚胎发育不等。在这一系列两部分的综述中，我们将重点介绍鲜为人知的炎症小体，如 NLRP6（非经典炎症小体激活）、NLRP9（限制轮状病毒在肠上皮细胞中的感染）、NLRX1（炎症的负调节剂）、NLRC5（调节抗原呈递）和 NLRP7（细菌脂蛋白的感应）。虽然 NLRP3 的功能已经了解，但这些研究较少的炎症小体的功能在很大程度上尚未研究。鉴于经过十年的研究，仍然发现新的炎症小体和新的炎症小体激活剂，这表明 NLR 领域还有很多需要我们去发现。只有了解 NLR 家族的所有成员，我们才能在未来有针对性地对它们进行治疗。
