Characterisation of lymphocyte function during tissue regeneration and natural ageing

组织再生和自然衰老过程中淋巴细胞功能的表征

• 批准号: BB/W001780/1
• 负责人: Rebecca Richardson
• 金额: $ 72.32万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW001780%2F1
• 关键词: Characterisation; lymphocyte; function; during; tissue

The completion of this project will help us to understand the effect adaptive immune cells have after a tissue is injured. We are born with cells of our innate immune system but our adaptive immune system develops over time and "learns" and "remembers" pathogens we encounter throughout our lives. The adaptive immune response is vital for fighting off many different infections and is made up of several different types of specialist cells which work together to protect us. Cells of our innate immune system, such as neutrophils and macrophages, fight infections too but are also vital in the response to tissue damage, helping injuries to heal in many different ways. The function of both our innate and adaptive immune system can decline as we get older, potentially affecting how well we can heal after injury. Some animals, such as zebrafish, are able to fully replace cells that were damaged or died as a result of an injury, without forming permanent scars, and innate immune cells like macrophages are vital for allowing this to happen. This suggests that understanding cells of the zebrafish immune system may hold the key to encouraging cells and organs of other animals to repair better or even regenerate. Certain types of adaptive immune cells (lymphocytes) influence these innate immune cells and this can both help and hinder the response to injury. Whether these lymphocytes are helpful or harmful to injury repair depends on several different factors, such as the type of cell being studied, the organ they are in or the type of injury, but we do not fully understand all these complex factors. For a long time it was thought that animals such as zebrafish had a less complex immune system than us and that was a reason why they can regenerate but mammals like us can't. However, we now know that zebrafish have very similar immune cells to us and we have shown that zebrafish lymphocytes also respond to an injury. The more we can learn about how zebrafish immune cells, including lymphocytes, can benefit regeneration the closer we could be to understanding how natural regeneration works and finding ways to encourage our cells to regenerate too. Currently, there have been very few studies into lymphocytes in any animals that can regenerate and so this project aims to address this gap in our knowledge. We will thoroughly map the different lymphocytes that respond to different types of injury in an adult zebrafish, investigate the effect of the loss of these cells on injury repair and regeneration and evaluate what happens to these cells as the fish get older. The completion of this project would provide much more information on how all different types of immune cells work together to facilitate tissue regeneration in zebrafish, helping us to identify better ways to promote injury repair in all animals.

该项目的完成将有助于我们了解适应性免疫细胞在组织损伤后的作用。我们生来就有先天免疫系统的细胞，但我们的适应性免疫系统随着时间的推移而发展，并“学习”和“记住”我们一生中遇到的病原体。适应性免疫反应对于抵抗许多不同的感染至关重要，它由几种不同类型的专门细胞组成，它们共同保护我们。我们先天免疫系统的细胞，如中性粒细胞和巨噬细胞，也可以对抗感染，但在对组织损伤的反应中也至关重要，以多种不同的方式帮助损伤愈合。随着年龄的增长，我们的先天免疫系统和适应性免疫系统的功能都会下降，这可能会影响我们受伤后的愈合情况。一些动物，如斑马鱼，能够完全取代因损伤而受损或死亡的细胞，而不会形成永久性疤痕，而巨噬细胞等先天免疫细胞对于实现这一目标至关重要。这表明，了解斑马鱼免疫系统的细胞可能是鼓励其他动物的细胞和器官更好地修复甚至再生的关键。某些类型的适应性免疫细胞（淋巴细胞）影响这些先天免疫细胞，这既可以帮助也可以阻碍对损伤的反应。这些淋巴细胞对损伤修复是有益还是有害取决于几个不同的因素，例如所研究的细胞类型，它们所在的器官或损伤类型，但我们并不完全了解所有这些复杂的因素。很长一段时间以来，人们认为像斑马鱼这样的动物的免疫系统没有我们复杂，这就是为什么它们可以再生，而像我们这样的哺乳动物却不能。然而，我们现在知道斑马鱼有与我们非常相似的免疫细胞，我们已经证明斑马鱼的淋巴细胞也会对损伤做出反应。我们对斑马鱼免疫细胞（包括淋巴细胞）如何促进再生的了解越多，我们就越接近了解自然再生是如何工作的，并找到鼓励我们的细胞再生的方法。目前，很少有研究表明任何动物的淋巴细胞都可以再生，因此该项目旨在解决我们知识中的这一空白。我们将彻底绘制成年斑马鱼中对不同类型损伤做出反应的不同淋巴细胞，研究这些细胞的损失对损伤修复和再生的影响，并评估随着鱼类年龄的增长，这些细胞会发生什么。该项目的完成将提供更多关于所有不同类型的免疫细胞如何共同促进斑马鱼组织再生的信息，帮助我们确定更好的方法来促进所有动物的损伤修复。