The role of Interleukin-21 in the pathogenesis of autoimmune diabetes

T细胞是我们血液（白色血细胞）的组成部分，也是人体抵抗感染的防御系统（称为免疫力）的主要组成部分。如果没有T细胞，我们将无法抵抗外来因子的感染，如病毒，细菌和真菌。自身免疫性（1型）糖尿病是一种疾病，其中T细胞攻击我们自己的胰岛自身组织，就像它们是外来的一样。与胰腺胰岛发生反应的T细胞会破坏产生胰岛素的β细胞，使胰腺无法再产生胰岛素。糖尿病是一种危及生命的疾病，因为胰岛素是一种激素，使人们能够从食物中获得能量。1型糖尿病通常在儿童时期被诊断出来，为了生存，必须每天通过注射或通过泵给予胰岛素。不幸的是，服用胰岛素不能治愈糖尿病，人们继续遭受影响大多数重要器官的广泛并发症。白细胞介素-21（IL-21）是一种可溶性蛋白质，由细胞产生，使它们能够与其他细胞沟通。IL-21帮助细胞产生引起炎症的因子，并协助清除体内的病毒和细菌。然而，我们的研究表明，IL-21是破坏β细胞并导致糖尿病的T细胞发育的主要因素。我们的研究表明IL-21在自发性1型糖尿病的重要小鼠模型中过表达。我们已经分离出导致糖尿病的T细胞，并表明它们与其他T细胞的区别在于非常高水平的IL-21受体。该项目的重点是导致糖尿病的IL-21反应性T细胞，旨在确定细胞因子IL-21引起破坏性免疫反应的机制以及调节其产生的方法。该项目将基础科学应用于1型糖尿病的重要公共卫生问题，以制定治疗干预策略。

T cells are a component of our blood (white blood cells) and a major component of the body's defense system against infection, known as immunity. Without T cells, we would fail to resist infection by foreign agents, such as viruses, bacteria and fungi. Autoimmune (type 1) diabetes is a disease in which T cells attack our own pancreatic islet self tissues as if they were foreign. T cells that react against the islets of the pancreas cause destruction of the insulin producing beta cells so that the pancreas can no longer make insulin. Diabetes is a life-threatening disease because insulin is a hormone that enables people to get energy from food. Type 1 diabetes is usually diagnosed in childhood and insulin must be administered daily by injection or through a pump in order to survive. Unfortunately, taking insulin doesn t cure diabetes and people continue to suffer from an extensive list of complications affecting most vital organs. Interleukin-21 (IL-21) is a soluble protein that is produced by cells enabling them to communicate with other cells. IL-21 helps cells to produce factors that cause inflammation and assist in clearance of viruses and bacteria from the body. However, our studies show that IL-21 is a major factor in the development of the T cells that destroy beta cells and cause diabetes. Our studies show that IL-21 is over-expressed in an important murine model of spontaneous type-1 diabetes. We have isolated the T cells that cause diabetes and show that they are distinguished from other T cells by very high levels of the receptor for IL-21. This project focuses on the IL-21-responsive T cells that cause diabetes and aims to determine the mechanisms by which the cytokine IL-21 causes destructive immune responses and ways to modulate its production. This project applies basic science to the important public health issue of type 1 diabetes for the development of therapeutic intervention strategies.