How inflammatory resolution shapes long-term tissue immunity

炎症消退如何塑造长期组织免疫力

• 批准号: BB/X016854/1
• 负责人: Derek Gilroy
• 金额: $ 160.69万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX016854%2F1
• 关键词: How; inflammatory; resolution; shapes; long

Inflammation is a protective response to infection and injury. However, once its job is done it's imperative that inflammation then switches off. This can be best exemplified by a bee sting where skin becomes hot, red, swollen and painful, the so-called four cardinal signs of inflammation. However, within hours or certainly a day, the heat, redness, swelling and pain goes away. This latter process is called inflammatory resolution. Importantly, resolution of acute inflammation is a natural sequence of events that, until now, was believed to lead the affected tissues back to the physiological and immunological state they experienced before inflammation occurred. However, we propose that this is not the case, and that resolution triggers a series of local clinically silent, but immunologically active events that are essential for maintaining the long-term immune health and well-being of the infected/damaged tissue. The aim of this proposal, therefore, is to study these novel post-inflammatory resolution processes and understand how they immunologically enhance tissues for prolonged and improved immune protection. The experiments proposed here will describe a new area of immune activity that extends long after the outwards sign of heat, redness, swelling and pain have resolved with a key role in maintaining lifelong heathy ageing and well-being in terms of shaping more efficient responses to secondary and subsequent infections. Consequently, it will describe new immune processes whose dysregulation arising from old age, pathogenic infections, environmental influences may become dysregulated driving aberrant immune responses and shortening human and animal life span. Consequently, we envision using this knowledge to optimise immune responses to infection without the need for antimicrobials and the problems of antimicrobial resistance.

炎症是对感染和损伤的保护性反应。然而，一旦它的工作完成，炎症就必须停止。最好的例子就是被蜜蜂蜇伤，皮肤变得又热、又红、又肿、又痛，即所谓的四大炎症症状。然而，几个小时甚至一天之内，发热、发红、肿胀和疼痛就会消失。后一个过程称为炎症消退。重要的是，急性炎症的消退是一个自然的事件序列，迄今为止，人们认为它可以使受影响的组织恢复到炎症发生前所经历的生理和免疫状态。然而，我们认为情况并非如此，该解决方案会引发一系列局部临床上无声但免疫活跃的事件，这些事件对于维持受感染/受损组织的长期免疫健康和福祉至关重要。因此，该提案的目的是研究这些新颖的炎症后消退过程，并了解它们如何从免疫学角度增强组织，从而延长和改善免疫保护。这里提出的实验将描述一个新的免疫活动领域，该领域在发热、发红、肿胀和疼痛等外在症状消失后仍会持续很长时间，在维持终生健康衰老和福祉方面发挥着关键作用，对继发性和后续感染形成更有效的反应。因此，它将描述新的免疫过程，其因年老、病原体感染、环境影响而引起的失调可能会导致异常的免疫反应并缩短人类和动物的寿命。因此，我们设想利用这些知识来优化对感染的免疫反应，而不需要抗菌药物和抗菌药物耐药性问题。