The role of endogenous glucocorticoids in regulating dendritic cell function in vivo

内源性糖皮质激素在体内调节树突状细胞功能的作用

• 批准号: G0601183/1
• 负责人: Ronjon Chakraverty
• 金额: $ 81.36万
• 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: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0601183%2F1
• 关键词: role; endogenous; glucocorticoids; regulating; dendritic

Vaccines are hugely important in the fight against infections. However, vaccines against many infections are ineffective and we are interested in finding ways to boost their activity. Vaccines may require special immune cells, called dendritic cells, to become activated. Thus, one reason why vaccines may not work is that these cells do not become activated enough. We have found that dendritic cells produce large amounts of steroids and that this may prevent them from becoming activated. The dendritic cells contain an enzyme that produces the steroid. Although these findings are very obvious when we culture dendritic cells in a test tube, it is now very important to work out what role this enzyme has in preventing immune responses following a vaccination. This requires that we perform experiments in mice, in which the gene that makes the enzyme has been ?knocked out?. In this case, we can take a mouse that is normal in every respect other than the fact that it cannot make the enzyme. We predict that responses to vaccination will be much better in mice that lack the enzyme in their dendritic cells. If so, this will be important, because new drugs have been developed that can block the enzyme from working. Thus, it may be possible to give a vaccine and an enzyme-stopping drug at the same time in order to get a better response.

疫苗在对抗感染方面非常重要。然而，针对许多感染的疫苗是无效的，我们有兴趣找到提高其活性的方法。疫苗可能需要特殊的免疫细胞，称为树突状细胞，被激活。因此，疫苗可能不起作用的一个原因是这些细胞没有被充分激活。我们发现树突状细胞产生大量的类固醇，这可能会阻止它们被激活。树突细胞含有一种产生类固醇的酶。虽然当我们在试管中培养树突状细胞时，这些发现是非常明显的，但现在非常重要的是要弄清楚这种酶在预防疫苗接种后的免疫反应中的作用。这就要求我们在小鼠中进行实验，其中产生酶的基因已经被？晕过去了？在这种情况下，我们可以拿一只在各方面都正常的老鼠，除了它不能制造酶的事实。我们预测，在树突细胞中缺乏这种酶的小鼠对疫苗接种的反应会更好。如果是这样的话，这将是重要的，因为已经开发出可以阻止酶工作的新药。因此，有可能同时给予疫苗和酶抑制剂，以获得更好的反应。