In MS, cells of the immune system invade the brain and spinal cord and cause tissue damage that leads to reduced brain and spinal cord function. Potential new treatments include drugs that can block the passage of the cells of the immune system into the brain and spinal cord that promote inflammation.
In this project, Ms Megan Monaghan will investigate certain markers on the surface of immune cells called CD4+ T cells. These markers, called chemokine receptors, help regulate the migration and activation of immune cells in response to inflammation, infection, and injury. She is particularly interested in identifying additional markers on these cells to see whether they are a specific type of immune cell that causes damage, called Th17 cells.
She will also use cutting-edge technology to create a detailed picture of the type of CD4+ T cells that infiltrate the brain and spinal cord.
This information will be invaluable for the design of next generation therapeutics that selectively block movement of inflammatory T cells into the brain in MS.
Ms Monaghan has identified several genes that may play a role in the migration of CD4+ T cells into the brain and spinal cord. These genes, which are higher in inflammatory CD4+ T cells and not in other CD4+ T cells that resolve inflammation, need further investigation to determine their contribution to disease progression. Further study is needed to find out if blocking the proteins these genes produce will slow down or stop disease progression.
Ms Monaghan found that a number of communication pathways (different ways cells talk to each other through proteins) are increased between infiltrating inflammatory CD4+ T cells and immune cells that normally reside in the brain. These pathways are a potential target for blocking inflammatory cells from moving into the brain.
Ms Monaghan has also analysed infiltrating CD4+ T cells of the brain and spinal cord at a tissue level. She aims to see where they may enter the brain and spinal cord to cause disease, where they move to once they have entered, how they communicate with cells in the brain and spinal cord, and what genes they express to do so. This will reveal how cells communicate and move within lesions and provide insight into how these cells develop and contribute to disease progression.
Over the next 12 months, Ms Monaghan will continue investigating the characteristics and behaviour of inflammatory CD4+ T cells and resident immune cells in the brain.
Updated 31 March 2025
Dr Ian Comerford
Professor Shaun McColl
Dr Stephen Pederson
$105,000
2024
3 years
Current project
