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

Project description

Studying the immune system’s role in neurodegenerative diseases

Neurodegenerative diseases (NDDs) affect over 55 million people worldwide, a number expected to triple in the coming decades. These conditions, marked by cognitive decline and motor deficits, have long been linked to the nervous system. However, recent advances reveal the immune system’s role in the brain, with immune cells now recognised as participants in neural homeostasis. Supported by the Marie Skłodowska-Curie Actions programme, the NKT-in-NDD project, led by experts from the University of Copenhagen, investigates the interaction between neurons and immune cells. By studying the CD1d gene, expressed by neurons, the project aims to explore how immune responses contribute to NDDs, potentially opening doors to new treatment options.

Objective

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.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

KOBENHAVNS UNIVERSITET
Net EU contribution

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€ 247 553,28
Address
NORREGADE 10
1165 KOBENHAVN
Denmark

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Region
Danmark Hovedstaden Byen København
Activity type
Higher or Secondary Education Establishments
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Total cost

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