Inflammasomes are cytoplasmic multiprotein complexes comprising a sensor protein, inflammatory caspases, and in some but not all cases an adapter protein connecting the two. They can be activated by a repertoire of endogenous and exogenous stimuli, leading to enzymatic activation of canonical caspase-1, noncanonical caspase-11 (or the equivalent caspase-4 and caspase-5 in humans) or caspase-8, resulting in secretion of IL-1β and IL-18, as well as apoptotic and pyroptotic cell death. Appropriate inflammasome activation is vital for the host to cope with foreign pathogens or tissue damage, while aberrant inflammasome activation can cause uncontrolled tissue responses that may contribute to various diseases, including autoinflammatory disorders, cardiometabolic diseases, cancer and neurodegenerative diseases. Therefore, it is imperative to maintain a fine balance between inflammasome activation and inhibition, which requires a fine-tuned regulation of inflammasome assembly and effector function. Recently, a growing body of studies have been focusing on delineating the structural and molecular mechanisms underlying the regulation of inflammasome signaling. In the present review, we summarize the most recent advances and remaining challenges in understanding the ordered inflammasome assembly and activation upon sensing of diverse stimuli, as well as the tight regulations of these processes. Furthermore, we review recent progress and challenges in translating inflammasome research into therapeutic tools, aimed at modifying inflammasome-regulated human diseases.

炎性小体是细胞质多蛋白复合物，包含传感器蛋白、炎性半胱天冬酶，以及在某些但并非全部情况下连接两者的衔接蛋白。它们可以被一系列内源性和外源性刺激激活，导致经典 caspase-1、非经典 caspase-11（或人类中等效的 caspase-4 和 caspase-5）或 caspase-8 的酶促激活，从而导致分泌IL-1β 和 IL-18，以及细胞凋亡和焦亡细胞死亡。适当的炎症小体激活对于宿主应对外来病原体或组织损伤至关重要，而异常的炎症小体激活可能导致不受控制的组织反应，可能导致多种疾病，包括自身炎症性疾病、心脏代谢疾病、癌症和神经退行性疾病。因此，必须维持炎症小体激活和抑制之间的良好平衡，这需要对炎症小体组装和效应功能进行微调。最近，越来越多的研究重点关注炎症小体信号传导调节的结构和分子机制。在本综述中，我们总结了在理解感知不同刺激时的有序炎症小体组装和激活以及这些过程的严格监管方面的最新进展和仍然存在的挑战。此外，我们回顾了将炎症体研究转化为治疗工具的最新进展和挑战，旨在改变炎症体调节的人类疾病。