Investigating a novel inhibitory signaling mechanism that represses T cell-driven CNS autoimmunity

Principal Investigator: Dr. Manu Rangachari

Affiliation: Université Laval

Term: April 1, 2017 – March 31, 2020

Funding: $299,259

Keywords: T cells, progressive MS, neuroimmunology, cytokines, serpine1

Summary:

  • Serpine1 is a protein that has been shown to reduce damage to the myelin caused by the harmful T cells from the immune system in an animal that mimics multiple sclerosis (MS)-like disease.
  • How Serpine1 exhibits its function on MS is unknown.
  • The research team will:
    • Examine proteins that are interacting with Serpine1 on harmful T cells of the immune system.
    • Delineate if Serpine1 exhibits its effects on the immune or nervous system in MS
    • Determine if Serpine-1 is involved in secondary progressive forms of the disease

Project Description:

Loss of myelin, covering on the nerve fibers, contributes to MS disease. The focus of Dr. Manu Rangachari’s research program is to identify genes that can lessen the immune attack against myelin. His research team has already found a specific gene called Serpine1 reduces damage to the myelin caused by the harmful T cells from the immune system in an animal that mimics MS disease. The goal of the current research project is to further delineate how Serpine1 works in MS. As MS is a disease involving both the immune and nervous systems, the research team will also determine which system Serpine1 exhibits its beneficial effects on. A current approved MS drug called fingolimod (Gilenya) is suggested to turn on the expression of Serpine1 and this might explain how fingolimod improves MS. Dr. Rangachari’s research team plans to understand this process further. In the past year, the research team has found that Serpine1 is important for the function of a protein that sits on the surface of T cells and is known to reduce inflammation. Furthermore, Dr. Rangachari and his team have established links between the function of Serpine1 and specific molecules that reside inside T cells themselves. Future work will attempt to study whether Serpine1 can also improve the symptoms of secondary progressive-like disease in an animal model of MS that was developed by the Rangachari lab.

Potential Impact: This work will help in understanding the function of a gene, Serpine1, that may reduce the severity of MS, and may be assessed further as a potential target for MS therapies.

Project Status: In Progress

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