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Regulation of EAE by skin immunization with self-peptide

自肽皮肤免疫调节EAE

基本信息

批准号：
7682025
负责人：
Margaret S. Bynoe
金额：
$ 38.5万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-15 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7682025
关键词：
Acute Animal Model Antigens Attenuated Autoantigens Autoimmune Diseases Blood - brain barrier anatomy C57BL/6 Mouse CD4 Positive T Lymphocytes Cells Central Nervous System Diseases Cessation of life Chronic Clinical Demyelinating Diseases Demyelinations Dendritic Cells Development Disease Dose Drug usage Encephalomyelitis Excision Experimental Animal Model Experimental Autoimmune Encephalomyelitis Goals Immune Immune Tolerance Immune response Immune system Immunization In Vitro Infiltration Inflammation Inflammatory Interleukin-10 Knowledge Lymphocyte Mediating Modeling Multiple Sclerosis Mus Myelin Myelin Basic Proteins Neuraxis Neuronal Dysfunction Oligodendroglia Paralysed Pathology Patients Peptides Peripheral Physiological Process Production Range Recurrent disease Regulation Regulatory Element Relapse Reporter Role Skin Source Staging T-Cell Receptor T-Lymphocyte Testing Thinking Tissues Toxin Transgenic Mice Ursidae Family Work cytokine human langerin intravital microscopy migration mouse model neuron loss prevent response skin patch therapy design

项目摘要

Multiple sclerosis (MS) is an inflammatory attack on the central nervous system (CNS) that results in extensive demyelination and loss of neuronal function that often leads to death. Experimental autoimmune encephalomyelitis (EAE) is the animal model for MS. This proposal will examine the regulation of the immune system response by epicutaneous (skin) immunization with self-antigen. Epicutaneous immunization is a process whereby, a skin patch soaked in antigen, in this case the CNS antigen myelin oligodendrocyte gylcpprotein (MOG), is applied to the shaved skin of mice prior to inducing EAE with the same antigen. We have recently shown that when we carry out epicutaneous immunization or skin patching with MOG in C57BL/6 mice prior to EAE induction that these mice are protected from developing EAE. Most importantly, when we apply epicutaneous immunization to mice after they develop EAE, mice with mild EAE are protected, but not mice with severe EAE. We observed that the CD4 T cells from mice that are protected from EAE produced high levels of IL-10 and they can transfer protection to na¿ve recipient mice. We also found that the epidermal dendritic cells in the skin that captured antigen from the patch can suppress EAE when they are isolated from the skin after epicutaneous immunization and transferred into na¿ve recipient mice. The goal of this proposal is set out in three specific aims that will determine 1) whether epicutaneous immunization/skin patching with MOG can ameliorate ongoing EAE in mice and reduce or prevent relapses; 2) determine whether tolerance mediated by CD4 T cells in mice epicutaneously immunized with MOG is dependent on IL-10 and 3) determine the role of epidermal dendritic cells in epicutaneous immunization-induced tolerance. These studies will serve to advance our knowledge of autoimmune disease regulation both at the peripheral level and at the CNS level and could be beneficial to MS and other autoimmune diseases.

多发性硬化症（MS）是中枢神经系统（CNS）的炎性发作，其导致广泛的脱髓鞘和神经元功能丧失通常导致死亡。实验性自身免疫性脑脊髓炎（EAE）是MS的动物模型。本建议将研究免疫调节通过用自身抗原进行表皮（皮肤）免疫的系统应答。皮肤免疫是一种这个过程中，皮肤贴片浸泡在抗原，在这种情况下，中枢神经系统抗原髓鞘少突胶质细胞在用相同抗原诱导EAE之前，将gylcpprotein（MOG）应用于小鼠剃光的皮肤。我们最近表明，当我们进行表皮免疫或皮肤贴敷MOG，在EAE诱导之前，C57 BL/6小鼠被保护免于发展EAE。最重要的是，当我们对发生EAE的小鼠进行表皮免疫时，轻度EAE的小鼠受到保护，但对患有严重EAE的小鼠没有影响。我们观察到来自受保护免于EAE的小鼠的CD 4 T细胞，产生高水平的IL-10，它们可以将保护作用转移到幼稚的受体小鼠。我们还发现皮肤中捕获贴片抗原的表皮树突状细胞在感染时可以抑制EAE 在表皮免疫后从皮肤分离并转移到未处理的受体小鼠中。的目标该建议在三个具体目标中列出，其将确定1）表皮免疫/皮肤用MOG贴敷可以改善小鼠中正在进行的EAE并减少或预防复发; 2）确定是否在用MOG上表皮免疫的小鼠中由CD 4 T细胞介导的耐受依赖于IL-10，以及3）确定表皮树突状细胞在表皮免疫诱导的耐受中的作用。这些研究将有助于提高我们对自身免疫性疾病调节的认识，无论是在外周水平，可能对MS和其他自身免疫性疾病有益。