Investigating CD1d-dependent neuronal activation of natural killer T cells and its impact on neurodegenerative disease

ended

Neurodegenerative diseases (NDDs) are a broad category of neurological maladies, typically characterized by cognitive decline and motor deficits. NDDs affect over 55 million individuals worldwide, a number that is expected to triple over the following decades. Until recently, the brain was considered immune-privileged, but emerging scientific advancements in the field of neuroimmunology show that immune cells reside within and even infiltrate the central nervous system (CNS). Despite ever-growing evidence illuminating the critical interplay between the nervous and immune system in maintaining neural homeostasis, research efforts have been limited in this scope. We recently identified that an immune-related gene, CD1d, is expressed by neurons. CD1d is recognized by natural killer T (NKT) cells, generally inducing an immunosuppressive response. We found that selective knockout of CD1d in neurons led to NDD development in mice. We also gathered biocomputational evidence from both human and mouse brains showing that neurons near the choroid plexus have the highest CD1d expression. These preliminary findings inspired the NKT-in-NDD project with the following three aims: (1) To determine whether CD1d-expressing neurons can sufficiently activate NKT cells (2) To examine the impact of CD1d-dependent neuronal activation of NKT cells on inflammatory conditions and NDDs (3) To verify whether CD1d is expressed by neurons localized near the choroid plexus As an expert in neurological maladies, I will join forces with Prof. Shohreh Issazadeh-Navikas, a leader in the neuroimmunology field, to tackle this interdisciplinary project at the Biotechnology Research & Innovation Centre (BRIC) at the University of Copenhagen (UCPH) in Denmark. Together, we will address various gaps in the fields of immune cell biology, neuroimmunology, and neurodegeneration. The neuroimmune insight developed from this project may expand current treatment options for NDDs.