Data_Sheet_1_A Mathematical Model for DC Vaccine Treatment of Type I Diabetes.pdf

Type I diabetes (T1D) is an autoimmune disease that can be managed, but for which there is currently no cure. Recent discoveries, particularly in mouse models, indicate that targeted modulation of the immune response has the potential to move an individual from a diabetic to a long-term, if not permanent, healthy state. In this paper we develop a single compartment mathematical model that captures the dynamics of dendritic cells (DC and tDC), T cells (effector and regulatory), and macrophages in the development of type I diabetes. The model supports the hypothesis that differences in macrophage clearance rates play a significant role in determining whether or not an individual is likely to become diabetic subsequent to a significant immune challenge. With this model we are able to explore the effects of strengthening the anti-inflammatory component of the immune system in a vulnerable individual. Simulations indicate that there are windows of opportunity in which treatment intervention is more likely to be beneficial in protecting an individual from entering a diabetic state. This model framework can be used as a foundation for modeling future T1D treatments as they are developed.

一型糖尿病（T1D）是一种自身免疫性疾病，尽管可以对其进行管理，但截至目前尚无治愈方法。近期的研究发现，特别是在小鼠模型中，针对免疫反应的精准调节有可能将个体从糖尿病状态转变为长期乃至永久的健康状态。在本文中，我们开发了一个单室数学模型，以捕捉树突状细胞（DC 和 tDC）、T 细胞（效应细胞和调节细胞）以及巨噬细胞在 T1D 发生发展过程中的动态变化。该模型支持如下假说：巨噬细胞清除率的不同在决定个体是否可能因重大免疫挑战而患上糖尿病方面起着重要作用。利用这一模型，我们得以探究加强易感个体免疫系统抗炎成分的影响。模拟结果表明，存在治疗干预的时机窗口，此时干预更有可能保护个体免于进入糖尿病状态。该模型框架可作为一种基础，用于未来 T1D 治疗方法的建模，随着治疗方法的发展而不断演进。