DRiPs致病性T细胞与胰腺CUZD-1蛋白双靶向Smart-DDS诱导免疫耐受治疗1型糖尿病的研究

最新研究证明抗原通过各种翻译后修饰形成的非传统表位是1型糖尿病（T1D）胰岛β细胞破坏始动和进展的关键。免疫治疗已成为自身免疫病研究的热点。目前针对T1D免疫治疗均是全身用药，药物到达胰腺直接作用于致病性T细胞的剂量低。我们前期研究证明纳米药物输送系统（DDS）为T1D诱导免疫耐受提供了有效手段。因此，我们拟设计一种新的针对核糖体缺陷产物（DRiPs）抗原特异性的T细胞，并筛选出胰腺特异性表达的蛋白CUZD-1，构建T细胞胰腺双靶向的磁性纳米Smart-DDS。以期其通过空间控制的方式，在有效降低给药剂量和频率的同时，靶向目标器官后释放和维持有效的药物负荷。我们从细胞、动物及人的水平多层次验证Smart-DDS靶向定位释放的能力，明确其对胰岛致病性T细胞抑制作用及对自身免疫糖尿病进程的影响；探讨其诱导免疫耐受的机制。本研究将Smart-DDS引入免疫治疗为T1D的精准治疗提供新的思路。

Non-conventional epitopes modified by various translations, play a key role in the occurrence and progression in type 1 diabetes (T1D). Recently, immunotherapy has become a hotspot in the field of autoimmune diseases. All the immunotherapies for T1D are systemic drugs, traditional medicine into the body does not directly access to pancreatic cells. Our preliminary study has proved that the nano-drug delivery system (DDS) provides new hope for induced antigen-specific immunological tolerance. Therefore, we intend to design a new magnetic nano-Smart-DDS targeted to the pancreas for DRiPs epitope specific T cells. It is hoped that the drug dose and frequency can be reduced and the effective drug load can be maintained by targeting organs in a spatially controlled manner. The ability of Smart-DDS to target the pancreas and location are verified from cells, animals and human levels. Then we determine the inhibition of antigen-specific T cells and the effects on disease process. Also, we explored the mechanism of induced immune tolerance. The purpose of this study is to demonstrate that Smart-DDS could induce tolerance in T1D. It will explore new ideas of clinical immunotherapy for T1D.