What role do natural killer cells play in MS?

Dr Nicole Fewings

Westmead Institute for Medical Research, NSW

| Better treatments | Immunology | Project | 2018 | Investigator Led Research |
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Summary

Natural killer (NK) cells are responsible for killing harmful cells in the body. This includes the body’s own cells that are infected with viruses, and other immune cells that inappropriately attack our own body (autoimmune cells). Previous work has suggested that in some people with MS, the killing power of NK cells is reduced. In a laboratory model of MS, this reduced function of NK cells is associated with increased MS relapses.

In this Project Grant Dr Fewings and her team will first analyse NK cells in MS in a more detailed way than has ever been conducted before, to better understand the changes in NK cells in MS. She will also determine if NK cells from people with MS are able to kill cells infected with viruses or activated immune cells (including the autoimmune cells that drive MS) in the laboratory. Of particular interest are cells infected with the Epstein Barr virus (EBV) which has been implicated in increased risk of MS.

A number of drugs that enhance the function of NK cells have been approved to treat cancer. Dr Fewings will investigate if these drugs have the potential to be repurposed for use in people with MS, to improve the function of NK cells to kill EBV- infected cells or toxic immune cells.

Progress to Date

Dr Fewings and her team designed and developed a new test to compare different subsets of NK cells in great detail. This technique (called “high dimensional flow cytometry”) involves passing blood cells past a laser that allows them to detect over 20 different properties of each cell at once, combined with a complex analysis pipeline. This work has been presented at a number of international conferences.

By comparing NK cells from people with and without MS, Dr Fewings has found that numbers of a specific type of immature NK cell are reduced in people with S. Across all NK cells, a marker of NK “killing power” was also reduced in MS, and a scientific manuscript describing this subset is currently in preparation.

Dr Fewings has also generated a model system of EBV infection in the laboratory, where she can drive the EBV-infected cells to be susceptible to killing by NK cells. Her team is generating a large bank of EBV-infected cells, with matching NK cells also collected. Going forward, they will use this system to see whether NK cells from people with MS have reduced capacity to kill EBV-infected cells, and whether the killing capacity can be restored using current cancer therapies, which if successful, could inform the development of new therapies.

Dr Fewings and her team have also developed multiple collaborations as a result of this work, one of which is looking to link up with Prof Georges Grau to examine NK cells in response to different MS treatments.

Updated: 17 May 2021

Updated: 05 January, 2018

Investigator

  • Dr Nicole Fewings, Westmead Institute for Medical Research, NSW

Co-investigator

  • Professor David Booth, Westmead Institute for Medical Research, NSW
  • Associate Professor Golo Ahlenstiel, Westmead Institute for Medical Research, NSW
  • Professor Steve Vucic, Westmead Institute for Medical Research, NSW

Grant Awarded

  • Project Grant

Total Funding

  • $216,000

Duration

  • 4 years

Funding Partner

  • Trish MS Research Foundation
  • MS Angels Sydney
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What role do natural killer cells play in MS?