ICES-based Pulsed Field Electromagnetic Field Therapy for Autoimmunity

摘要/摘要 人类自身免疫性疾病，如1型糖尿病(T1D)，具有异质性和复杂性的特点 推动免疫病理学的事件。为了应对这种疾病预防和治疗的异质性，我们 需要多种具有不同作用机制的免疫疗法。考虑到这一点，我们R21的目标是 建议建立概念证明，脉冲电磁场(PEMF)疗法是一种有效的 有选择地抑制正在进行的自身免疫，并重新建立自我耐受的方法。微/纳米电流 在适当的条件下，PEMF在体内诱导可以改变细胞的性质。不同类型的PEMF 已经成功和安全地应用于临床；然而，用于自身免疫的PEMF尚未被 测试过。 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 (冰块)。ICES的特性导致电磁脉冲被认为与自然电信号非常相似 既增强生物效应又增强安全性的事件。概述了三个目标，使用NOD小鼠作为 建立T1D自发模型，建立基于ICES的PEMF对自身免疫的调节作用。在……里面 目的1，研究ICES对细胞特异性T细胞反应性的致耐受作用。《目标2》将专注于 测定ICES对树突状细胞成熟和功能的影响。在AIM 3中，ICES诱导的免疫调节 将进行探索，并调查对获得性免疫的影响。这项工作有望为今后的工作奠定基础 对于未来的研究：1)进一步定义ICES具体和一般PEMF的机制 调节免疫效应器，以及2)测试ICES预防和/或治疗T1D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.