Summary: Researchers uncover beneficial effects of immune cells in myelin repair that could reverse myelin damage in multiple sclerosis.
Source: Queen’s University Belfast.
Queen’s University Belfast scientists have discovered that specific cells from the immune system are key players in brain repair.
The research study, led by Dr Yvonne Dombrowski and Dr Denise Fitzgerald at the Wellcome-Wolfson Institute for Experimental Medicine at Queen’s University Belfast, is being hailed as a landmark study in unravelling the mysteries of how the brain repairs damage. This is crucial in the fight against MS, which affects 2.3 million people world-wide and over 4,500 people in Northern Ireland.
MS is the most common neurological disease affecting young adults and is the result of damage to myelin, the protective sheath surrounding nerve fibres of the central nervous system – the brain, spinal cord and optic nerve. In MS, the immune system wrongly attacks the myelin sheath covering nerve fibres in the brain and spinal cord, which can lead to symptoms such as vision loss, pain, fatigue and paralysis.
Until now, medical treatment could limit relapses but could not reverse the damage already done by the condition. The exciting aspect of this new research is that the team have uncovered beneficial effects of immune cells in myelin repair that have potential to reverse myelin damage. The study was an international collaboration including experts in Cambridge, San Francisco, Edinburgh, Maynooth and Nice.
This is a fundamental breakthrough that could revolutionise the treatment of debilitating neurological disorders such as Multiple Sclerosis (MS).
The research breakthrough, which has been published today in Nature Neuroscience, shows that a protein made by certain cells within the immune system triggers the brain’s stem cells to mature into oligodendrocytes that repair myelin.
The discovery means that researchers can now use this new knowledge to develop medicines which will boost these particular cells and develop an entirely new class of treatments for the future.
Speaking about the importance of the new research, Dr Dombrowski, who is the lead author of the report, explained: “At Queen’s we are taking a unique and fresh approach to uncover how the immune system drives brain repair. This knowledge is essential to designing future treatments that tackle neurological diseases, such as MS, in a new way – repairing damage rather than only reducing attacks. In the future, combining these approaches will deliver better outcomes for patients.”
Senior author of the study, Dr Denise Fitzgerald from Queen’s, experienced a condition similar to MS, called Transverse Myelitis when she was 21 and had to learn to walk again.
Commenting on the findings, Dr Fitzgerald said: “This pioneering research, led by our team at Queen’s, is an exciting collaboration of top scientists from different disciplines at Cambridge, San Francisco, Edinburgh, Maynooth and Nice. It is by bringing together these experts from immunology, neuroscience and stem cell biology that we have been able to make this landmark discovery.
“This is an important step forward in understanding how the brain and spinal cord is naturally repaired and opens up new therapeutic potential for myelin regeneration in patients. We continue to work together to advance knowledge and push the boundaries of scientific knowledge for the benefits of patients and society, in a bid to change lives for the better, across the globe.”
Dr Sorrel Bickley, Head of Biomedical Research at the MS Society, said: “MS is an unpredictable and challenging condition, and we are committed to driving forward research to find effective treatments for everyone. This exciting study gives us an important understanding of how myelin repair can be promoted, which could open up new areas for treatment development. We welcome this international collaboration led by Northern Ireland, where rates of MS are amongst the highest in the world.”
Funding: This work was supported by a number of funders including the BBSRC, Wellcome Trust, Leverhulme Trust and the UK MS Society.
Source: Queen’s University Belfast
Image Source: NeuroscienceNews.com image is adapted from the Queen’s University Belfast press release.
Original Research: Abstract for “Regulatory T cells promote myelin regeneration in the central nervous system” by Yvonne Dombrowski, Thomas O’Hagan, Marie Dittmer, Rosana Penalva, Sonia R Mayoral, Peter Bankhead, Samara Fleville, George Eleftheriadis, Chao Zhao, Michelle Naughton, Rachel Hassan, Jill Moffat, John Falconer, Amanda Boyd, Peter Hamilton, Ingrid V Allen, Adrien Kissenpfennig, Paul N Moynagh, Emma Evergren, Bernard Perbal, Anna C Williams, Rebecca J Ingram, Jonah R Chan, Robin J M Franklin & Denise C Fitzgerald in Nature Neuroscience. Published online March 13 2017 doi:10.1038/nn.4528
Regulatory T cells promote myelin regeneration in the central nervous system
Regeneration of CNS myelin involves differentiation of oligodendrocytes from oligodendrocyte progenitor cells. In multiple sclerosis, remyelination can fail despite abundant oligodendrocyte progenitor cells, suggesting impairment of oligodendrocyte differentiation. T cells infiltrate the CNS in multiple sclerosis, yet little is known about T cell functions in remyelination. We report that regulatory T cells (Treg) promote oligodendrocyte differentiation and (re)myelination. Treg-deficient mice exhibited substantially impaired remyelination and oligodendrocyte differentiation, which was rescued by adoptive transfer of Treg. In brain slice cultures, Treg accelerated developmental myelination and remyelination, even in the absence of overt inflammation. Treg directly promoted oligodendrocyte progenitor cell differentiation and myelination in vitro. We identified CCN3 as a Treg-derived mediator of oligodendrocyte differentiation and myelination in vitro. These findings reveal a new regenerative function of Treg in the CNS, distinct from immunomodulation. Although the cells were originally named ‘Treg’ to reflect immunoregulatory roles, this also captures emerging, regenerative Treg functions.
“Regulatory T cells promote myelin regeneration in the central nervous system” by Yvonne Dombrowski, Thomas O’Hagan, Marie Dittmer, Rosana Penalva, Sonia R Mayoral, Peter Bankhead, Samara Fleville, George Eleftheriadis, Chao Zhao, Michelle Naughton, Rachel Hassan, Jill Moffat, John Falconer, Amanda Boyd, Peter Hamilton, Ingrid V Allen, Adrien Kissenpfennig, Paul N Moynagh, Emma Evergren, Bernard Perbal, Anna C Williams, Rebecca J Ingram, Jonah R Chan, Robin J M Franklin & Denise C Fitzgerald in Nature Neuroscience. Published online March 13 2017 doi:10.1038/nn.4528