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

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它们活性的方法。疫苗可能需要特殊的免疫细胞，称为树突状细胞，才能激活。因此，疫苗可能不起作用的一个原因是这些细胞没有得到足够的激活。我们发现，树突状细胞会产生大量类固醇，这可能会阻止它们被激活。树突状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，这些发现非常明显，但现在非常重要的是要弄清楚这种酶在预防接种疫苗后的免疫反应中起到什么作用。这需要我们在老鼠身上进行实验，在这些实验中，制造酶的基因已经被敲除。在这种情况下，我们可以选择一只在所有方面都正常的小鼠，除了它不能制造这种酶的事实。我们预测，在树突状细胞中缺乏这种酶的小鼠，对疫苗的反应将会好得多。如果是这样的话，这一点将是重要的，因为已经开发出可以阻止这种酶发挥作用的新药。因此，为了获得更好的反应，同时给予疫苗和酶停止药物是可能的。

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.