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.

炎症是对感染和伤害的保护反应。但是，一旦完成工作，炎症就必须关闭。蜜蜂的刺痛可以最好地举例说明，皮肤变热，红色，肿胀和痛苦，即所谓的四个炎症的主要标志。但是，在几个小时或肯定的一天之内，热，发红，肿胀和疼痛消失了。后一个过程称为炎症分辨率。重要的是，急性炎症的分辨率是自然事件的序列，到目前为止，人们据信将受影响的组织带回了他们在炎症发生前经历的生理和免疫学状态。但是，我们认为情况并非如此，并且解决方案触发了一系列局部临床沉默但具有免疫活性事件，这些事件对于维持长期免疫健康和感染/受损组织的福祉至关重要。因此，该提案的目的是研究这些新颖的炎性后分辨率过程，并了解它们如何在免疫学上增强组织，以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区域，该区域在热，发红，肿胀和疼痛的外向迹象很长时间内延伸，在维持终生的Heathy老化和健康状况方面的关键作用在塑造对二次感染和后续感染方面的反应方面发挥了关键作用。因此，它将描述新的免疫过程，其失调是由老年，致病性感染，环境影响引起的，可能会变成失调的驱动异常免疫反应并缩短人类和动物的生命跨度。因此，我们设想使用这些知识来优化对感染的免疫反应，而无需抗菌剂和抗菌耐药性问题。