ICES-based Pulsed Field Electromagnetic Field Therapy for Autoimmunity

总结/摘要 人类自身免疫性疾病如1型糖尿病（T1 D）的特征在于异质性和复杂性， 推动免疫病理学的事件。为了处理这种异质性，以预防和治疗疾病，我们 需要具有不同作用机制的多种免疫疗法。考虑到这一点，我们的R21的目标 建议是建立概念验证，脉冲电磁场（PEMF）治疗是一种有效的 方法选择性抑制正在进行的自身免疫，并重建自身耐受性。微/纳电流 在适当条件下由PEMF在体内诱导的细胞毒性可以改变细胞特性。不同类型的PEMF 已经成功和安全地应用于临床;然而，使用PEMF治疗自身免疫性疾病还没有被证实。 测试. 在这项研究中，我们使用了一种独特的PEMF，称为感应耦合电刺激 （ICES）. ICES的特性导致电磁脉冲被认为与天然电信号非常相似 增强生物效应和安全性的事件。概述了三个目的，采用NOD小鼠和 T1 D的自发模型，以建立基于ICES的PEMF调节自身免疫的适用性。在 目的1，研究ICES对T细胞特异性T细胞反应性的致耐受性作用。目标2将侧重于 确定ICES对树突状细胞成熟和功能的影响。目的3 ICES诱导的免疫调节 将进行探索，并研究对获得性免疫的影响。这项工作有望建立一个基础 未来的研究：1）进一步定义ICES具体的机制，以及一般的PEMF 调节免疫效应物，和2）测试ICES预防和/或治疗T1 D的临床应用，以及 其他自身免疫性疾病和免疫驱动的病理。

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.