Innate immune regulation of neuroinflammation

项目摘要 中枢神经系统(CNS)的炎症与疾病的发生和发展密切相关 多发性脱髓鞘和神经退行性疾病的进展，包括多发性硬化(MS)， 帕金森氏病、阿尔茨海默病、肌萎缩侧索硬化症和一般年龄相关疾病 因此，迫切需要开发新的方法来预防、限制或扭转认知衰退。 神经炎。基础、翻译和临床研究表明，T细胞可能是 中枢神经系统中的炎症反应，但促进或抑制这些反应的机制仍不清楚。 这项研究建议的基本焦点是：(I)询问一种新的途径，通过它 先天免疫系统控制CNS中的T细胞反应，(Ii)了解这些调节 细胞相互作用，以及(Iii)确定是否有可能利用这个或相关的途径 对神经炎的治疗益处。我们将采用创新的方法和开发新的工具来 解决这些知识上的根本差距，并在可能的情况下，将我们的发现从小鼠转化为 临床定义的患者样本。这些研究的结果将增进我们对 促进或抑制中枢神经系统中促炎性T细胞反应的通路，并可能引发 新一代预防、治疗或治愈脱髓鞘的治疗策略 和神经退行性疾病。

PROJECT ABSTRACT Inflammation in the central nervous system (CNS) is causally associated with the pathogenesis and progression of multiple demyelinating and neurodegenerative diseases, including Multiple Sclerosis (MS), Parkinson's Disease, Alzheimer's Disease, Amyotrophic Lateral Sclerosis, and general age-associated cognitive decline Therefore, there is an urgent need to develop novel approaches to prevent, limit or reverse neuroinflammation. Basic, translation and clinical studies indicate that T cells can be major drivers of inflammation in the CNS, but the mechanisms promoting or inhibiting these responses remain poorly defined. The fundamental focus of this research proposal is to: (i) interrogate a novel pathway by which the innate immune system controls T cell responses in the CNS, (ii) understand the regulation of these cellular interactions, and (iii) define whether it is possible to harness this or related pathways for therapeutic benefit in neuroinflammation. We will employ innovative approaches and develop new tools to address these fundamental gaps in knowledge, and where possible, translate our findings from mice into clinically defined patient samples. Results from these studies will advance our understanding of the pathways that promote or inhibit pro-inflammatory T cell responses in the CNS, and could provoke the next generation of novel preventative, therapeutic or curative treatment strategies for demyelinating and neurodegenerative diseases.