Immunoregulation of Experimental Autoimmune Myasthenia Gravis

实验性自身免疫性重症肌无力的免疫调节

基本信息

批准号：
7384319
负责人：
Matthew Nicholas Meriggioli
金额：
$ 17.72万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7384319
关键词：
Activated Lymphocyte Adoptive Transfer Affect Aftercare Agrin American Animals Antibodies Antibody Formation Antigen Targeting Antigen-Presenting Cells Antigens Autoantibodies Autoantigens Autoimmune Diseases Autoimmune Process Autoimmune thyroiditis Autoimmunity B-Lymphocytes Basic Science Biological Assay Cell physiology Cells Cholinergic Receptors Clinical Complement Dendritic Cells Deposition Development Disease Effectiveness of Interventions Epitopes Equilibrium Experimental Autoimmune Myasthenia Gravis Generations Granulocyte-Macrophage Colony-Stimulating Factor Hematopoietic Cell Growth Factors ITGAX gene Immune Immune System and Related Disorders Immune response Immunity Immunization Immunodominant Epitopes Immunoglobulin Class Switching Immunoglobulin G Immunologics Immunology Immunosuppressive Agents In Vitro Interleukin-10 Interleukin-3 Investigation Laboratories Laboratory Research Learning Lymphocyte Mediating Mentors Microbiology Modeling Molecular Morphology Mus Muscle Myasthenia Gravis Nature Neuromuscular Diseases Neuromuscular Junction Nicotinic Receptors Organ Other Therapy Patients Personal Satisfaction Phenotype Physicians Play Population Predisposition Principal Investigator Production Program Development Protein Subunits Proteins Reaction Regulation Research Research Personnel Resistance Risk Role Scientist Severity of illness Skeletal Muscle Sodium Channel Specificity Splenocyte Staging Symptoms T-Cell Proliferation T-Cell Receptor T-Lymphocyte T-Lymphocyte Subsets Testing Therapeutic Tissues Toxic effect Translations Vasoactive Intestinal Peptide attenuation autoreactivity base bench to bedside career clinically relevant connectin cytokine design immunoregulation in vivo insight neuroimmunology peripheral membrane protein 43K prevent programs receptor research study response skills synthetic peptide therapy design voltage

项目摘要

DESCRIPTION (provided by applicant): This proposal describes a five year career development program aimed at providing the applicant with the requisite skills and background for an academic career as a clinician-scientist in neuroimmunology and neuromuscular disease. The principal investigator is currently a practicing academic neuromuscular physician and clinical researcher specializing in autoimmune myasthenia gravis (MG). He now proposes to shift his career course to supplement this clinical background with basic science research skills allowing for bench-to-bedside translation of clinically relevant laboratory discoveries. Supervised laboratory research will take place under the direction of Dr. Bellur Prabhakar, Chair of the Department of Microbiology and Immunology and a recognized leader in the field of immunology, who will mentor the principal investigator's scientific development. Dr. Premkumar Christadoss will serve as co-mentor, contributing his recognized expertise in experimental autoimmune myasthenia gravis (EAMG). Autoimmune MG is a prototypic antibody-mediated autoimmune disorder in which the target antigen, the skeletal muscle acetylcholine receptor (AChR) is well-characterized. MG is an ideal model of autoimmunity, and insights relevant to MG may be applied to other autoimmune diseases. Research in this proposal will focus on studies examining immunoregulatory mechanisms in EAMG aimed at identifying clinically relevant antigen-specific treatment. Preliminary studies by the principal investigator have shown that treatment with the hematopoietic growth factor, GM-CSF, has a pronounced suppressive effect on the induction of EAMG. The proposed experiments will, therefore, examine the therapeutic potential of GM-CSF in treating established EAMG. The Specific Aims include: 1) Examination of the therapeutic potential of GM-CSF in EAMG and characterization of its effects on AChR-specific immune responses. 2) Exploration of the role of regulatory T cell subsets in the GM-CSF-induced suppression of EAMG, the mechanism of their effect and their role in the suppression of pathogenic anti-AChR antibody production. 3) Investigation of GM-CSF's local effects on immune molecules and other NMJ proteins in EAMG mice. These studies are expected to provide significant insights into the nature and mechanisms of the effects of GM-CSF-induced regulatory cells in EAMG and provide additional information regarding EAMG's immunopathogenesis.

描述（由申请人提供）：该提案描述了一项为期五年的职业发展计划，旨在为申请人提供作为神经免疫学和神经肌肉疾病的临床医生科学家学术生涯所必需的技能和背景。主要研究人员目前是一名实践学术神经肌肉医师和临床研究人员，专门从事自身免疫性肌无力的Gravis（MG）。现在，他建议通过基础科学研究技巧来改善自己的职业课程，以补充这种临床背景，以允许对临床相关的实验室发现的基准翻译。监督实验室研究将在微生物学和免疫学系主任贝鲁·普拉巴卡（Bellur Prabhakar）博士的指导下进行，并将在免疫学领域公认的领导者，他将指导首席研究者的科学发展。 Premkumar Christadoss博士将担任联合学者，并在实验性自身免疫性肌无松（EAMG）方面贡献了他公认的专业知识。自身免疫性MG是一种原型抗体介导的自身免疫性疾病，其中靶抗原，骨骼肌乙酰胆碱受体（ACHR）被充分表征。 MG是自身免疫性的理想模型，与MG相关的见解可能应用于其他自身免疫性疾病。该提案中的研究将重点介绍研究旨在鉴定临床相关抗原特异性治疗的EAMG中免疫调节机制的研究。首席研究者的初步研究表明，用造血生长因子GM-CSF治疗对EAMG的诱导具有明显的抑制作用。因此，提出的实验将检查GM-CSF在治疗已建立的EAMG方面的治疗潜力。具体目的包括：1）检查GM-CSF在EAMG中的治疗潜力及其对ACHR特异性免疫反应的影响的表征。 2）探索调节性T细胞子集在GM-CSF诱导的EAMG抑制，其作用机理及其在抑制致病性抗ACHR抗体产生中的作用的作用。 3）研究GM-CSF对EAMG小鼠中免疫分子和其他NMJ蛋白的局部影响。这些研究有望提供有关GM-CSF诱导的EAMG调节细胞作用的性质和机制的重大见解，并提供有关EAMG免疫发病发生的其他信息。