Innate immune regulation of neuroinflammation

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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.