ICES-based Pulsed Field Electromagnetic Field Therapy for Autoimmunity

基于 ICES 的自身免疫脉冲场电磁场治疗

基本信息

批准号：
10079462
负责人：
Roland M Tisch
金额：
$ 19.44万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-06 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10079462
关键词：
Antigens Autoimmune Diseases Autoimmunity Automobile Driving Biological Biophysical Process Cell Maturation Cell physiology Cells Clinic Complex Coupled Data Dendritic Cells Development Effectiveness Effector Cell Electric Stimulation Electromagnetic Fields Electromagnetics Electrostatics Eragrostis Event FOXP3 gene Foundations Future Goals Heterogeneity Human Human Activities Immune Immunotherapy Inbred NOD Mice Inflammation Insulin-Dependent Diabetes Mellitus Mediating Mind Modeling Molecular Nature Orthopedics Pathology Phenotype Physiologic pulse Prevention Property Proteins Pulse Rates Regulatory T-Lymphocyte Reporting Rest Safety Self Tolerance Shapes Signal Transduction Site T-Lymphocyte Testing Therapeutic Tissues Work acquired immunity autoreactivity base cell type clinical application combinatorial disease heterogeneity disorder prevention effector T cell humanized mouse immunopathology immunoregulation in vivo innovation insight islet nano novel pre-clinical prevent tool

项目摘要

SUMMARY/ABSTRACT Human autoimmune diseases such as type 1 diabetes (T1D) are characterized by heterogeneous and complex events driving immunopathology. To deal with this heterogeneity for disease prevention and treatment, we need a variety of immunotherapies with distinct mechanisms of action. With this in mind, the goal of our R21 proposal is to establish proof-of-concept that pulsed electromagnetic field (PEMF) therapy is an effective approach to selectively suppress ongoing autoimmunity, and reestablish self-tolerance. Micro/nano-currents induced in vivo by PEMF under the appropriate conditions can alter cellular properties. Different types of PEMF have been successfully and safely applied in the clinic; however, use of PEMF for autoimmunity has not been tested. For this study, we are using a unique type of PEMF referred to as inductively coupled electrical stimulation (ICES). Properties of ICES result in electromagnetic pulses believed to closely mimic native electrical signaling events that enhance both biological effects and safety. Three Aims are outlined, employing NOD mice a spontaneous model of T1D, to establish the applicability of ICES-based PEMF to modulate autoimmunity. In Aim 1, studies will define the tolerogenic effects of ICES on  cell-specific T cell reactivity. Aim 2 will focus on determining ICES effects on dendritic cell maturation and function. In Aim 3 ICES-induced immunoregulation will be explored, and effects on acquired immunity investigated. This work is expected to establish a foundation for future studies: 1) to further define the mechanisms by which ICES specifically, and PEMF in general regulate immune effectors, and 2) to test the clinical application of ICES to prevent and/or treat T1D, as well as other autoimmune diseases and immune-driven pathologies.

摘要/摘要人类自身免疫性疾病（例如1型糖尿病（T1D））的特征是异质和复杂驱动免疫病理学的事件。为了处理这种预防疾病和治疗的异质性，我们需要各种具有不同作用机理的免疫疗法。考虑到这一点，我们R21的目标建议是建立概念证明，即脉冲电磁场（PEMF）治疗是一种有效的有选择地抑制正在进行的自身免疫和重建自我耐受性的方法。微/纳米电流 PEMF在适当条件下诱导的体内会改变细胞特性。不同类型的PEMF 已成功地安全地应用于诊所；但是，将PEMF用于自身免疫性测试。对于这项研究，我们使用的是一种独特的PEMF，称为电感耦合电模拟（冰）。冰的特性导致电子脉冲据信密切模仿天然电信号传导增强生物效应和安全性的事件。概述了三个目标，采用点头小鼠A T1D的赞助模型，以建立基于ICE的PEMF调节自身免疫性的适用性。在 AIM 1，研究将定义IC的耐受作用对细胞特异性T细胞反应性的耐受作用。 AIM 2将重点关注确定冰对树突状细胞成熟和功能的影响。在AIM 3 ICE诱导的免疫调节中将探索，并对所研究的免疫学的影响。预计这项工作将建立基础对于未来的研究：1）进一步定义了特定的ICS和PEMF的机制调节免疫作用，2）测试IC的临床应用以预防和/或治疗T1D，以及其他自身免疫性疾病和免疫驱动的病理。