Summary
- Researchers co-funded by the National MS Society report study results indicating that “Tregs” – regulatory immune cells that are known to be dysfunctional in people with MS – play a role in promoting formation of new myelin following damage.
- The team also pinpointed a specific protein, CCN3, that was produced by Tregs and appears to be responsible for enhancing myelin regeneration.
- If the results are confirmed through further research, these basic laboratory studies could eventually be translated to promising new therapeutic approaches to stimulating myelin repair to restore function in people with MS.
- The team (Yvonne Dombrowski, PhD, Denise C Fitzgerald, PhD [Queen’s University Belfast] and international colleagues) published results in Nature Neuroscience (Published online, March 13, 2017).
Background: In MS, myelin, the material that surrounds and protects nerve fibers, is damaged in the brain and spinal cord, and so are the cells that make myelin, called oligodendrocytes. The attack on myelin is driven by specific immune cells called T cells. Other immune cells known as T regulatory cells, or Tregs, have the ability to regulate or suppress the immune attack. In people with MS, however, Tregs have been shown to be less able to perform this helpful function. Previous research has indicated a possible role of Tregs in tissue regeneration, so this team explored how Tregs might promote regeneration of myelin.
The Study: First, the team deleted Tregs from a mouse model in which myelin is damaged and then spontaneously repairs. In this model, immature oligodendrocytes were generated, but failed to mature into myelin-making cells. Formation of new myelin was substantially impaired. Administering Tregs to the mice, however, replenished the supply of mature oligodendrocytes.
Then, the team examined whether Tregs could promote myelination in healthy mouse brain tissue isolated in the laboratory. Oligodendrocytes and myelin formation increased in tissue treated with Tregs, significantly more than control tissue without them. Because there is no inflammation in this model, this suggests the Tregs were doing something directly to the oligodendrocytes to promote myelin repair.
Importantly, the team also pinpointed a specific protein, CCN3, that was produced by Tregs and appeared to be responsible for enhancing myelin regeneration. Although prior research has suggested a role for CCN3 in tissue regeneration, this is the first report of its role in the central nervous system, and the first report showing that Tregs produce this regenerative protein.
The team (Yvonne Dombrowski, PhD, Denise C Fitzgerald, PhD [Queen’s University Belfast] and international colleagues) published results in
Nature Neuroscience (
Published online, March 13, 2017)
. This work was supported by the UK MS Society, National MS Society, NIH and Wellcome Trust, among others.
Next Steps: If the results are confirmed through further research, these basic laboratory studies could eventually be translated to promising new therapeutic approaches to stimulating myelin repair to restore function in people with MS.
Read more about efforts to stimulate repair in MS
Read about the event that inspired Dr. Fitzgerald to conduct research on myelin repair