Understanding the function of dendritic cells in the chicken - a species lacking lymph nodes.

了解鸡（缺乏淋巴结的物种）中树突状细胞的功能。

• 批准号: BB/E008941/1
• 负责人: Peter Kaiser
• 金额: $ 56.4万
• 依托单位: The Pirbright Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE008941%2F1
• 关键词: Understanding; function; dendritic; cells; chicken

The UK poultry industry faces increasing challenges in the 21st century. Many of the drugs used to control diseases in poultry are being withdrawn from use. At the same time, improving welfare standards mean that the industry is becoming more free-range. But the downside is that free-range chickens face higher rates of disease challenge, for example through contact with wild birds. One answer to this problem is to develop novel vaccines. To do this, we need to understand the bird's immunity to disease, so that we can identify ways to control that response. We already know that in birds and mammals the immune response can be divided into two arms - the innate response and the adaptive response. The latter is a very specific response, which hopefully leads to immune 'memory', in other words the ability to respond rapidly to subsequent infections with the same pathogen. This is how vaccination works. The innate immune response is a generalised response that recognises components of a wide range of pathogens, for example, specific types of molecules in a bacterial coat. It serves two roles - it limits infection until the adaptive immune response can kick in, and also provides signals that control the adaptive immune response. The main link between the two responses is a specialised cell type, the dendritic cell or DC. These cells are 'professional antigen presenting cells'. They present 'antigen' (little bits of the pathogen) from pathogens to cells of the adaptive immune response, so they can be recognised as foreign, and provide signals to the same cells to help them respond in the correct way. To date, the function of DC have only been understood for a small number of mammalian species. We are the first people to have been able to grow chicken DC in the lab, and now wish to begin to understand their function. If we can understand how chicken DC work, then we can begin to figure out how we can manipulate them to give better responses to vaccines. We propose to determine how chicken DC respond to different pathogens, how they move around the body from the site of infection to the site of antigen presentation (in other words, to where they talk directly to the cells of the adaptive response), and how they control the cells of the adaptive immune response. From this should come clues as to which molecules are able to influence the function of chicken DC, and therefore which have the potential to act as vaccine adjuvants, in other words to give a stronger response to existing and novel vaccines, to give better protection to the pathogen the vaccine is designed against.

世纪英国家禽业面临着越来越多的挑战。许多用于控制家禽疾病的药物正在停止使用。与此同时，福利标准的提高意味着该行业正变得更加自由放养。但缺点是，自由放养的鸡面临更高的疾病挑战率，例如通过与野生鸟类接触。解决这个问题的一个办法是开发新的疫苗。要做到这一点，我们需要了解鸟类对疾病的免疫力，这样我们就可以找到控制这种反应的方法。我们已经知道，在鸟类和哺乳动物中，免疫反应可以分为两类-先天性反应和适应性反应。后者是一种非常特异性的反应，有望导致免疫“记忆”，换句话说，能够对随后的相同病原体感染迅速作出反应。疫苗就是这样起作用的。先天性免疫反应是一种广泛的反应，可以识别各种病原体的成分，例如细菌外壳中的特定类型的分子。它有两个作用-它限制感染，直到适应性免疫反应可以启动，并提供控制适应性免疫反应的信号。这两种反应之间的主要联系是一种专门的细胞类型，树突状细胞或DC。这些细胞是“专职抗原呈递细胞”。它们将病原体的“抗原”（病原体的一小部分）呈递给适应性免疫反应的细胞，因此它们可以被识别为外来物，并向相同的细胞提供信号，帮助它们以正确的方式做出反应。迄今为止，DC的功能仅在少数哺乳动物物种中被了解。我们是第一个能够在实验室中培养鸡DC的人，现在希望开始了解它们的功能。如果我们能理解鸡DC是如何工作的，那么我们就可以开始弄清楚我们如何操纵它们来对疫苗产生更好的反应。我们建议确定鸡DC如何响应不同的病原体，它们如何在体内从感染部位移动到抗原呈递部位（换句话说，到它们直接与适应性反应细胞对话的地方），以及它们如何控制适应性免疫反应的细胞。从这一点可以看出，哪些分子能够影响鸡DC的功能，因此哪些分子有可能作为疫苗佐剂，换句话说，对现有的和新的疫苗产生更强的反应，对疫苗所针对的病原体提供更好的保护。

项目成果

Chicken interleukin-21 is costimulatory for T cells and blocks maturation of dendritic cells.

鸡白细胞介素 21 对 T 细胞具有共刺激作用，并阻止树突状细胞的成熟。

• DOI: 10.1016/j.dci.2011.08.013
• 发表时间: 2012
• 期刊: Developmental and comparative immunology
• 影响因子: 2.9
• 作者: Rothwell L

Chicken CCR6 and CCR7 are markers for immature and mature dendritic cells respectively.

• DOI: 10.1016/j.dci.2010.12.015
• 发表时间: 2011-05
• 期刊: Developmental and comparative immunology
• 影响因子: 2.9
• 作者: Zhiguang Wu;Tuanjun Hu;P. Kaiser