Development and functions of tissue resident memory T cells during EAE

EAE 期间组织驻留记忆 T 细胞的发育和功能

基本信息

批准号：
10549845
负责人：
Estelle Bettelli
金额：
$ 21.66万
依托单位：
BENAROYA RESEARCH INST AT VIRGINIA MASON
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：
2022-02-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10549845
关键词：
Address Antigens Attenuated Autoimmunity Axon Biology Blood Brain CD4 Positive T Lymphocytes CD8B1 gene CNS autoimmune disease CNS autoimmunity Cells Central Nervous System Central Nervous System Diseases Central Nervous System Infections Cerebrospinal Fluid Characteristics Chronic Circulation Complex DNA cassette Demyelinations Development Disease Disease Progression Disease model Disease remission Enterobacteria phage P1 Cre recombinase Experimental Autoimmune Encephalomyelitis Future Genetic Granulocyte-Macrophage Colony-Stimulating Factor Helper-Inducer T-Lymphocyte Homing IL17 gene Immune Immune system Immunization Individual Inflammation Interferon Type II Interleukin-13 Interleukin-4 Invaded Kinetics Knock-in Knowledge Longevity Mediating Memory Modeling Mouse Strains Multiple Sclerosis Mus Myelin Neurologic Dysfunctions Pattern Peripheral Phenotype Play Property Relapse Reporting Role Site Spinal Cord T memory cell T-Lymphocyte Tamoxifen Time Tissues Toxin Variant antigen challenge autoreactivity brain parenchyma cytokine disability effective therapy effector T cell genomic locus inducible Cre insight memory CD4 T lymphocyte multiple sclerosis patient multiple sclerosis treatment novel novel therapeutics pathogen red fluorescent protein secondary lymphoid organ selective expression tissue resident memory T cell tool transcription factor

项目摘要

Project Summary Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by demyelination, axonal loss, and progressive disability. The disease can follow a relapsing remitting or a more chronic course. Similarly, experimental autoimmune encephalomyelitis (EAE) models are characterized by CNS inflammation and demyelination, and each recapitulate some aspects of MS. Although there is a wealth of knowledge regarding the association of different circulating T helper (Th) subsets with multiple sclerosis (MS), there is a paucity of information regarding the characteristics and functions of tissue resident memory T cells (TRM) which have been recently identified in the central nervous system (CNS) and the cerebrospinal fluid (CSF) of MS patients. To begin to address this gap, we have used a newly developed mouse strain to identify, track, characterize and eliminate TRMs during the course of experimental autoimmune encephalomyelitis (EAE). We propose that autoreactive CNS CD4+ TRM express a unique set of markers that distinguish them from other circulating central memory T cells and play an important role in disease progression. Using our newly developed tools, we will characterize the distribution, kinetic and characteristics of CD4+ TRM cells during EAE, establish whether they recirculate and participate in disease progression and relapses during EAE. The completion of this proposal will help us understand how memory T cells promote chronic autoimmunity and may lead to the development of novel therapies for MS.

项目摘要多发性硬化症（MS）是中枢神经系统（CNS）的自身免疫性疾病通过脱髓鞘，轴突损失和进行性残疾。该疾病可以遵循复发的恢复或更多慢性课程。同样，实验性自身免疫性脑脊髓炎（EAE）模型的特征是CNS 炎症和脱髓鞘，每种都概括了MS的某些方面。虽然有很多关于不同循环T辅助（Th）子集与多发性硬化症（MS）的关联的知识，关于组织驻留记忆T细胞的特征和功能的信息很少（TRM）最近在中枢神经系统（CNS）和脑脊液中鉴定出来的（TRM）（CSF）MS患者。为了开始解决这一差距，我们使用了新开发的鼠标菌株来识别，在实验性自身免疫性脑脊髓炎（EAE）过程中，轨道，表征和消除了TRM。我们建议自动反应性CNS CD4+ TRM表达一组独特的标记，将它们与其他标记区分开循环中央记忆T细胞并在疾病进展中起重要作用。使用我们新开发的工具，我们将表征EAE期间CD4+ TRM细胞的分布，动力学和特征，建立它们是否在EAE期间再循环和参与疾病进展和复发。完成此完成建议将帮助我们了解记忆T细胞如何促进慢性自身免疫性，并可能导致开发MS的新型疗法。