T cells as modulators of microglia-mediated neurodegeneration in Niemann Pick type C (NPC) disease

The aim of our project is to study microglia – T cell interaction in the context of neurodegeneration and neuroinflammation. We will use our newly generated rodent Niemann-Pick type C (NPC) model recapitulating microglia-mediated neurodegeneration.

NPC is a rare progressive autosomal recessive lipid storage disorder largely caused by mutations in NPC1 gene that controls intracellular lipid homeostasis. It presents with complex visceral, neurological, and psychiatric symptoms that most often manifest at childhood age and rapidly progress to neurodegeneration and pre-mature death. There is currently no cure for this devastating form of childhood dementia. Neuroinflammation is one of the key pathological hallmarks of NPC that occurs prior to neurodegeneration. To determine the potential of the adaptive immune system to contribute to neuroinflammation and neurodegeneration, we will characterize the functional role of T cells on microglial phenotypes and NPC pathology in the rodent model and validate T cell-microglia interactions in human brain tissue. Results derived from this project will increase our mechanistic understanding of neuroinflammation in NPC and contribute to better evaluate its potential for therapeutic modulation.