操控PANoptosome:毫无根据的炒作还是人类免疫的新希望?
Manipulating the PANoptosome: baseless hype or a newfound hope for human immunity?
作者信息
Enuganti Dhruv, Bandharam Navya, Narra Bhavishya, Yata Vinod Kumar, Kolliputi Narasaiah
机构信息
Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd, Tampa, FL, 33612, USA.
Department of Pharmacology, School of Allied and Healthcare Sciences, Malla Reddy University, Hyderabad, Telangana, 500100, India.
出版信息
Apoptosis. 2025 Jul 23. doi: 10.1007/s10495-025-02152-7.
The human immune system uses many tactics to protect itself from harm, attempting to restore homeostatic conditions. Of these tactics, the primary defense mechanism which is activated is innate immunity. Innate immunity employs phagocytic cells which contain Pattern Recognition Receptors (PRRs) on their surface to promote attachment to certain molecules on pathogens and/or generally damaged/injured cells, which contain Pattern-Associated Molecular Patterns (PAMPs) and Damage/Danger-Associated Molecular Patterns (DAMPs), respectively. DAMPs and PAMPs associate with PRRs in host cells. The interaction between innate immune cells and pathogenic molecular patterns triggers programmed cell death (PCD) pathways; the three main ones being pyroptosis, apoptosis, and necroptosis. Historically, the three were thought to operate autonomously, with no intersection between any, but emerging research has brought a new concept into the limelight: PANoptosis. PANoptosis is now recognized as a distinct, innate immune-regulated inflammatory cell death pathway orchestrated by the PANoptosome, a multiprotein complex that integrates molecular components from pyroptosis, apoptosis, and necroptosis, yet functions independently of them. This integrated pathway plays a crucial role in eliminating infected or damaged cells and modulating immune responses. PANoptosis must be tightly regulated at all times, as any abnormality may increase the chances of a multitude of chronic, severe, and potentially terminal illnesses. Developing a better understanding of PANoptosis offers a promising set of possibilities within immunology research and medicine. By elucidating the relationship between the PCD pathways and how they come together to form a PANoptosome, better targets for treatment can be isolated and integrated into new innovative treatments for a wide range of ailments. This review addresses the mechanisms surrounding PANoptosis and its possible implications for the future of medicine, carrying the potential to bridge the gap of knowledge that exists surrounding complex immunological illnesses and also identifying new markers and significant factors contributing to a treatment/cure.
人类免疫系统运用多种策略来保护自身免受伤害,试图恢复体内平衡。在这些策略中,首先被激活的主要防御机制是固有免疫。固有免疫利用吞噬细胞,这些细胞表面含有模式识别受体(PRR),以促进与病原体上的某些分子和/或通常受损/受伤细胞上的分子结合,这些细胞分别含有模式相关分子模式(PAMP)和损伤/危险相关分子模式(DAMP)。DAMP和PAMP与宿主细胞中的PRR结合。固有免疫细胞与致病分子模式之间的相互作用触发程序性细胞死亡(PCD)途径;主要的三种途径是焦亡、凋亡和坏死性凋亡。从历史上看,人们认为这三种途径是独立运作的,彼此之间没有交集,但新兴研究使一个新的概念成为焦点:泛凋亡。现在人们认识到泛凋亡是一种由泛凋亡小体精心编排的独特的、固有免疫调节的炎症性细胞死亡途径,泛凋亡小体是一种多蛋白复合物,整合了来自焦亡、凋亡和坏死性凋亡的分子成分,但又独立于它们发挥作用。这种整合途径在清除受感染或受损细胞以及调节免疫反应方面起着关键作用。泛凋亡必须始终受到严格调控,因为任何异常都可能增加患多种慢性、严重和潜在致命疾病的几率。更好地理解泛凋亡为免疫学研究和医学提供了一系列有前景的可能性。通过阐明PCD途径之间的关系以及它们如何结合形成泛凋亡小体,可以分离出更好的治疗靶点,并将其整合到针对多种疾病的新型创新治疗方法中。本综述探讨了围绕泛凋亡的机制及其对医学未来的可能影响,有可能弥合围绕复杂免疫疾病存在的知识差距,并识别出新的标志物以及有助于治疗/治愈的重要因素。