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，炎症就必须关闭。这可以通过蜜蜂蜇伤最好地说明，皮肤变得热，红，肿和痛，所谓的炎症的四个主要标志。然而，在几个小时或一天内，热，发红，肿胀和疼痛消失。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，到目前为止，人们认为它会使受影响的组织恢复到炎症发生前的生理和免疫状态。然而，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免疫活性的事件，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的炎症后解决过程，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领域，该领域在热，发红，肿胀和疼痛的向外迹象已经解决后很长时间内延伸，在维持终身健康衰老和健康方面发挥关键作用，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，其由老年、病原性感染、环境影响引起的失调可能变得失调，从而驱动异常的免疫应答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，而不需要抗菌剂和抗菌素耐药性的问题。