SFB 1403: Cell Death in Immunity, Inflammation and Disease

细胞死亡是一个基本的生物过程，对维持组织稳态至关重要，在动物和植物的宿主-微生物相互作用和病原体防御中起着核心作用。最近发现的溶解性细胞死亡的分子控制途径，如坏死坏死、焦亡和铁亡，揭示了细胞可以在不同的调节细胞死亡（RCD）模式之间进行选择，并引发了细胞死亡在组织和有机体水平上的后果受到细胞死亡方式的深刻影响的概念。垂死的细胞通过与旁观细胞进行亲密的交叉对话来调节组织反应，但尚不清楚细胞死亡的类型如何决定这种相互作用的结果。虽然现在人们普遍认为不同的RCD通路具有不同的功能，但我们才刚刚开始了解它们各自的生理作用以及它们是如何相互联系的。此外，决定细胞是否死亡、何时死亡以及如何死亡的机制及其对周围组织的影响仍然知之甚少。本CRC的总体目标是了解多种形式的RCD在机体生理学和病理学中的调节机制以及功能和生理后果，特别关注免疫，炎症和宿主-微生物相互作用。在第一个资助期间，CRC研究人员的合作小组取得了重要发现，大大提高了我们对动物和植物中不同类型RCD调节机制的理解。此外，CRC研究人员在阐明RCD不同途径在免疫、炎症和疾病中的作用以及剖析其潜在机制方面取得了相当大的进展。通过大量的网络、教育和培训活动，我们促进和培养了一个高度协作的跨学科研究社区，使我们的中心成为一个国际知名的细胞死亡研究中心。在下一个资助期内，我们将进一步扩展和更新我们的计划，以解决细胞死亡研究中的基本问题。通过加深我们对不同形式的RCD在机体生理学和病理学中的调控和功能的理解，并剖析其潜在的机制，我们最终渴望为患者和经济上重要的作物的细胞死亡相关疾病提出新的基于知识的治疗方法。

Cell death is a fundamental biological process that is critical for the maintenance of tissue homeostasis and plays a central role in host-microbe interactions and pathogen defence in both animals and plants. The recent discoveries of molecularly controlled pathways of lytic cell death, such as necroptosis, pyroptosis and ferroptosis, revealed that cells can select between different modalities of regulated cell death (RCD) and instigated the concept that the consequences of cell death at the tissue and organismal levels are profoundly affected by the way a cell dies. Dying cells regulate tissue responses by engaging in an intimate cross-talk with bystander cells, yet it remains unclear how the type of cell death determines the outcome of this interaction. While it is now generally accepted that the different RCD pathways have distinct functions, we are only just beginning to understand their respective physiological roles and how these are interlinked with each other. Moreover, the mechanisms determining whether, when and how a cell dies and the effects this exerts on surrounding tissues remain poorly understood. The overarching goal of this CRC is to understand the mechanisms of regulation and the functional and physiological consequences of diverse forms of RCD in organismal physiology and pathology, with particular focus on immunity, inflammation and host-microbe interactions. During the first funding period, collaborative groups of CRC researchers made important discoveries that considerably advanced our understanding of the mechanisms regulating different types of RCD in animals and plants. Moreover, CRC investigators made considerable progress in elucidating the role of different pathways of RCD in immunity, inflammation and disease and dissecting the underlying mechanisms. Through a multitude of networking, educational and training activities, we promoted and fostered a highly collaborative inter-disciplinary research community establishing our CRC as an internationally prominent centre on cell death research. During the next funding period, we will further expand and update our program to address fundamental outstanding questions in cell death research. By advancing our understanding of the regulation and function of the different forms of RCD in organismal physiology and pathology and dissecting the underlying mechanisms, we ultimately aspire to propose new knowledge-based therapeutic approaches for cell death-related diseases in patients and in economically important crops.