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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.

项目总结