IL-1R1, MMP-9, and EAE

IL-1R1、MMP-9 和 EAE

基本信息

批准号：
10553700
负责人：
Ning Quan
金额：
$ 19.06万
依托单位：
FLORIDA ATLANTIC UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-21 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10553700
关键词：
Affect Animal Model Attenuated Autoantigens Autoimmune Autoimmune Process Autoimmunity Biology Blood - brain barrier anatomy Brain CNS autoimmune disease Cell physiology Cells Central Nervous System Clinical Collaborations Disease Endothelial Cells Endothelium Enterobacteria phage P1 Cre recombinase Experimental Autoimmune Encephalomyelitis Experimental Models Extracellular Matrix Foundations Future Gelatinase B Genetic Models Grant Immune Inflammatory Inhibition of Matrix Metalloproteinases Pathway Interleukin-1 Interleukin-1 Receptors Knock-out Leucocytic infiltrate Leukocytes Link Matrix Metalloproteinases Mediating Modeling Multiple Sclerosis Mus Myelin Sheath Pathogenesis Pathogenicity Peripheral Persons Play Process Role Signal Transduction System T-Cell Activation T-Lymphocyte Testing Tissues Visualization autoimmune inflammation autoreactivity brain endothelial cell cell type conditional knockout cytokine design drug development inhibitor multiple sclerosis treatment nervous system disorder novel therapeutic intervention recruit restoration targeted treatment tool

项目摘要

PROJECT SUMMARY Multiple sclerosis (MS) is a significant neurological disease affecting millions of people in the US. This disease is believed to be driven by autoimmune activities against the myelin sheath in the central nervous system. MS is modeled by the experimental autoimmune encephalomyelitis (EAE), which mimics many aspects of MS. Interleukin-1 (IL-1) signaling has been shown to be essential for the pathogenesis of EAE, but which cell-type specific IL-1 receptor mediated processes are required for EAE are unclear. In addition, matrix metalloproteinase 9 (MMP-9) is known to play an important role in mediating the breakdown of the blood brain barrier during EAE. Our preliminary results show endothelial IL-1 receptor type 1 (eIL-1R1) and T cell IL-1 receptor type 1 (TcIL-1R1) may both be required to mediate different aspects of the EAE pathogenesis, and IL-1R1 and MMP-9 may amplify each other’s function during EAE. This application is designed to: 1) Demonstrate eIL-1R1 and TcIL-1R1 combine to mediate EAE induction; 2) Identify the roles of MMP-9 in eIL-1R1 and TcIL-1R1 mediated autoimmune processes; and 3) Determine whether IL-1R1 and MMP-9 specific inhibitors synergistically block EAE induction and progression.

项目概要多发性硬化症 (MS) 是一种严重的神经系统疾病，影响着美国数百万人。这种疾病被认为是由针对髓鞘的自身免疫活动引起的 MS 是通过实验性自身免疫性脑脊髓炎建模的。 (EAE)，它模仿了白细胞介素 1 (IL-1) 信号传导的许多方面。对于 EAE 的发病机制至关重要，但细胞类型特异性 IL-1 受体介导 EAE 所需的过程尚不清楚。此外，基质金属蛋白酶 9 (MMP-9) 也不清楚。已知在 EAE 期间介导血脑屏障的破坏中发挥重要作用。我们的初步结果显示内皮 IL-1 受体 1 型 (eIL-1R1) 和 T 细胞 IL-1 受体 1 型 (TcIL-1R1) 可能都需要介导 EAE 发病机制的不同方面，而IL-1R1和MMP-9在EAE过程中可能会增强彼此的功能。旨在：1) 证明 eIL-1R1 和 TcIL-1R1 结合介导 EAE 诱导；2) 识别 MMP-9 在 eIL-1R1 和 TcIL-1R1 介导的自身免疫过程中的作用；3) 确定 IL-1R1 和 MMP-9 特异性抑制剂是否可以协同阻断 EAE 的诱导和进展。