The role of type 2 innate lymphoid cells in autoimmune islet infiltration and diabetes

1型糖尿病在英国和世界范围内是一个日益严重的问题，受影响的人数逐年增加。潜在的问题是免疫系统攻击并破坏胰腺中制造胰岛素的细胞。我们知道，一种名为T细胞的免疫细胞负责推动这一过程，但它并不是单独起作用的：需要许多不同类型的细胞之间的协调相互作用。了解这些不同类型的细胞在疾病过程中的作用对于我们设计以知情的方式干扰免疫介导的攻击的方法至关重要。在分析自身免疫性糖尿病患者胰腺中的免疫细胞时，我们最近发现了一个以前没有报道过的群体。这些所谓的“先天淋巴细胞”或ILC是该领域的新手，但在过去的几年里已经产生了很多令人兴奋的东西。它们是罕见的细胞，但似乎能够深刻地影响免疫反应--即它们超出自身重量。已经证明，它们可以改变T细胞的行为方式，指示它们分泌不同的产物，并改变正在发生的免疫反应的类型。我们有最新的数据表明，它们可以改变T细胞是否分泌一种我们知道与1型糖尿病的发生有关的IL-21。因此，ILC可能在决定针对胰腺的破坏性免疫反应中起关键作用。目前对ILC在1型糖尿病中的作用知之甚少，因为该区域完全没有研究。我们建议的实验将确定ILC如何在胰腺免疫反应的启动过程中影响T细胞，进而T细胞如何影响ILC本身。我们将利用我们初步数据中的线索和ILC领域的最新发现，提出ILC是对死亡的胰腺细胞做出反应还是与神经系统组件相互作用的问题。通过与ILC生物学领域的领先专家合作，我们将进行实验，直接测试ILC是否影响糖尿病的诱发或进展。重要的是，正在开发的一些针对1型糖尿病等自身免疫性疾病的治疗方法可能会对ILC和T细胞起作用。因此，了解ILC在疾病发展中是积极的还是消极的，以便正确使用这些药物是至关重要的。总体而言，这个项目将建立在我们小组令人兴奋的新数据的基础上，以确定新的参与者在免疫介导的胰腺攻击中的作用。

Type 1 diabetes is an increasing problem in the UK and worldwide, with rising numbers of people being affected year on year. The underlying problem is that the immune system attacks and destroys the cells that make insulin in the pancreas. We know that a type of immune cell called a T-cell is responsible for driving the process, however it does not work alone: coordinated interaction between a number of different cell types is required. Understanding the contribution of these different cell types to the disease process is vital for us to design ways to interfere with the immune-mediated attack in an informed way.While analysing the immune cells infiltrating the pancreas in autoimmune diabetes, we recently discovered a population that has not been reported here before. These so called "Innate Lymphoid Cells" or ILC are relative newcomers to the field but have generated lots of excitement over the last few years. They are rare cells, but appear capable of profoundly influencing immune responses - i.e. they punch above their weight. It has been shown that they can change the way T-cells behave, instructing them to secrete different products and alter the type of immune response that is occurring. We have very recent data showing that they can alter whether T-cells secrete something called IL-21 which we know is linked to the development of type 1 diabetes. It is therefore possible that ILC play a key role in determining whether a destructive immune response against the pancreas is mounted.At present nothing is known about the role of ILC in type 1 diabetes since the area is completely uninvestigated. Our proposed experiments will define how ILC affect T-cells during the initiation of an immune response in the pancreas, and in turn how the T-cells influence the ILCs themselves. We will use clues from our preliminary data, and the latest discoveries from the ILC field, to ask questions about whether ILC respond to dying pancreas cells or interact with nervous system components. By collaborating with leading experts in ILC biology, we will perform experiments to directly test whether ILC influence diabetes induction or progression. Importantly, some of the treatments being developed for autoimmune diseases like type 1 diabetes are likely to act on ILC as well as T-cells. It is therefore vital to understand whether ILC play a positive or negative role in disease development so that these drugs can be used correctly.Collectively this project will build on exciting new data from our group to define the role of a new player in the immune-mediated attack on the pancreas.