CD4 T cell differentiation and regulation in autoimmune diabetes

1型糖尿病是一种自身免疫性疾病，免疫系统的细胞攻击胰腺并阻止其产生胰岛素。即使新的胰岛素生成细胞作为移植提供，免疫系统也会简单地破坏它们。现有的药物可以抑制整个免疫系统，但这些药物会产生意想不到的副作用。成功治疗1型糖尿病的关键是确定导致疾病的细胞，这样就可以选择性地靶向治疗。我们在小鼠模型中进行了一项筛选，以确定导致糖尿病的免疫细胞的特征。这项工作产生了惊人的结果；这些细胞很明显是一个特殊的亚群，叫做滤泡辅助性T细胞。这种免疫细胞亚群可能导致糖尿病的可能性以前没有被探索过。这项工作旨在研究这些细胞是如何发育的，并确定靶向治疗这一亚群是否可以预防或逆转糖尿病。我们将探索是否可以在1型糖尿病患者的血液样本中检测到滤泡辅助性T细胞，并将利用小鼠糖尿病模型，以便我们可以测试靶向这些细胞是否有有益的效果。

Type 1 diabetes is an autoimmune disease in which cells of the immune system attack the pancreas and prevent it from producing insulin. Even if new insulin-producing cells are provided as a transplant, the immune system simply destroys these too. Medicines are available that suppress the entire immune system, but these have unwanted side effects. The key to successful treatment of type 1 diabetes is to pinpoint which cells cause disease so that these can be selectively targeted. We have performed a screen to characterise the immune cells that cause diabetes in a mouse model. This work has yielded a striking result; the cells are quite clearly a particular subset called follicular helper T cells. The possibility that this subset of immune cells could cause diabetes has not previously been explored. The proposed work seeks to investigate how these cells develop, and determine whether targeting this subset therapeutically can prevent or reverse diabetes. We will explore whether follicular helper T cells can be detected in blood samples from type 1 diabetes patients and will also take advantage of mouse diabetes models so we can test whether targeting these cells has beneficial effects.