Project R-14975

Identifying the molecular drivers of Treg loss-of-function during brain barrier transmigration (Research)

In efforts to find reparative strategies for brain damage, regulatory T cells (Tregs) have gained increased attention over the past few years. Next to their intrinsic capacity to dampen immune responses, Tregs are now attributed a pivotal role in response to brain trauma and even repair of damaged brain tissue. However, it remains unclear why brain-infiltrating Tregs fail to prevent disease progression in the context of inflammatory neurological disorders such as multiple sclerosis (MS). Our recent discoveries have pinpointed that Tregs lose their immunosuppressive capacity due to migration across the blood-brain barrier (BBB). Therefore, we aim to elucidate the interactions between Tregs and brain barrier cells, to identify novel therapeutic targets for neuroinflammatory disorders. Our proposed experiments will first extend our findings into other models of neuroinflammation/degeneration, to understand whether Treg loss-of-function is a common feature. Second, we will provide a full analysis of the interactions between Tregs and brain barrier cells. Finally, we will intervene with these interactions to provide proof-of-concept of a novel Tregbased therapy for neurodegenerative disorders.

14 June 2024 - 28 February 2027