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Immunoregulation in CNS remyelination

中枢神经系统髓鞘再生中的免疫调节

基本信息

批准号：
10432140
负责人：
Jeffrey K Huang
金额：
$ 34.02万
依托单位：
GEORGETOWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10432140
关键词：
Address Adult Affect Amino Acid Transporter Amino Acids Ammonia Astrocytes Axon Biochemical CD4 Positive T Lymphocytes Cell Differentiation process Cell Lineage Cell Proliferation Cell physiology Cells Chronic Cytomegalovirus Data Demyelinating Diseases Demyelinations Dissection Dyes Electron Microscopy Enzyme-Linked Immunosorbent Assay Enzymes FRAP1 gene Failure Fibroblasts Flow Cytometry Future Human Hydrogen Peroxide Immune Immunology procedure Inflammation Inflammatory Injections Interferon Type II Interleukin-17 Interleukins Keto Acids Knowledge Label Lead Lesion Lymphocyte Lymphocyte Function Lymphocyte Subset Lysophosphatidylcholines Mass Spectrum Analysis Mediating Methods Multiple Sclerosis Mus Myelin Natural regeneration Neuraxis Neutral Amino Acid Transport Systems Neutral Amino Acids Nude Mice Oligodendroglia Oxidases Patients Peripheral Blood Mononuclear Cell Pharmacology Phenylalanine Population Proliferating Proteins Proteomics Quantitative Reverse Transcriptase PCR Recombinants Regulation Resolution Role Signal Transduction Spinal Cord T-Lymphocyte Tamoxifen Testing Therapeutic Tissues Transcript Transplantation Wild Type Mouse amino acid metabolism antagonist disability immunoregulation improved in vivo loss of function macrophage metabolomics multiple sclerosis patient novel oligodendrocyte lineage progressive neurodegeneration remyelination repaired research and development success transcriptomics

项目摘要

Project Summary Failure to regenerate myelin in multiple sclerosis (MS) contributes to progressive axonal loss and accumulated disability. We have previously found that interleukin-four induced one (IL4i1), a macrophage-secreted immunoregulatory enzyme that serves to breakdown L-amino acids, modulates inflammation to promote remyelination in the mouse central nervous system (CNS). Moreover, we found that IL4i1 promotes remyelination by reducing pro-inflammatory CD4+ Th1 and Th17 cell activity in CNS lesions. Exactly how IL4i1 exerts its effect on the lesion microenvironment during remyelination remains unknown. However, the requirement for IL4i1 in remyelination suggests that a previously unknown mechanism involving amino acid metabolism operates in CNS lesions to control inflammation and promote repair. Here, we hypothesize that the regulation of amino acid metabolism in CNS lesions is critical for remyelination success. To this end, we will profile the levels of amino acids in CNS lesions over the course of remyelination by mass spectrometry analysis (Aim 1), determine if amino acid transport is required to regulate inflammation and remyelination (Aim 2), and determine if modulators of amino acid metabolism affects remyelination efficiency (Aim 3). The results of this study, if successful, will elucidate the role of amino acid metabolism on immune cells in CNS remyelination, and lead to future studies on modulators of amino acid metabolism as potential therapeutics for improving remyelination in MS.

项目总结