An international team of researchers led by the Karolinska Institutet in Sweden has discovered that a type of cell in the central nervous system known as oligodendrocytes may play a different role in the development of multiple sclerosis (MS) than previously thought. The results published in the journal Neuron, could open up new therapeutic approaches for MS.
MS is fueled by immune cells that attack oligodendrocytes and the myelin they produce, which is an insulating layer that encases nerve cells. These attacks disrupt the flow of information in the brain and spinal cord, causing nerve damage that triggers symptoms associated with MS, such as tremors and loss of gait.
Understanding which mechanisms influence MS risk is central to finding effective therapies. Previous genetic studies have found regions in the human genome that contain mutations (single nucleotide polymorphisms) that are associated with an increased risk of MS. Many of these regions are located near genes that are active in immune cells.
Open configuration of the genome
In this study, the researchers show in mouse and human brain samples that oligodendrocytes and their progenitors have an open genome configuration near immune genes and MS risk-associated regions. This suggests that the MS risk mutations may play a role in activating neighboring genes in oligodendrocytes and their progenitors, meaning they may play a more important role than previously thought in the development of MS.
Our results indicate that the risk of multiple sclerosis could manifest itself not only through malfunctioning of immune cells, but also of oligodendrocytes and their progenitor cells.”
Gonçalo Castelo-Branco, Professor, Institute of Medical Biochemistry and Biophysics, Karolinska Institutet
Gonçalo Castelo-Branco conducted the study with co-first authors Mandy Meijer, a PhD student, and Eneritz Agirre, a researcher.
“These results indicate that these cells can also serve as a target for therapeutic approaches in MS to prevent malfunctions that could be caused by these mutations.”
Meijer, M., et al. (2022) Epigenomic priming of immune genes implicates oligodendroglia in susceptibility to multiple sclerosis. Neuron. doi.org/10.1016/j.neuron.2021.12.034.