New MS research finds early immune activity in myelin cells
Early disease stages reveal immune-like shifts in oligodendrocytes in MS mice
- Oligodendrocytes in MS mice show immune-like activity early in the disease.
- These myelin-building cells can may play a role in inflammatory processes from early on.
- Future MS therapies may need to target specific oligodendrocyte subtypes.
Oligodendrocytes, the cells that build and repair myelin in the brain and spinal cord, may play a role in the inflammatory processes involved in multiple sclerosis (MS), even at the earliest stages of disease, according to a study in a mouse model.
“We found that oligodendrocytes transition to disease states already at early stages in this mouse model of MS,” Gonçalo Castelo-Branco, PhD, a co-author of the study and professor at the Karolinska Institutet in Sweden, said in an institute news story.
The study, “Distinct transcriptomic and epigenomic responses of mature oligodendrocytes during disease progression in a mouse model of multiple sclerosis,” was published in Nature Neuroscience.
How inflammation affects myelin and the cells that make it
In MS, inflammation in the brain and spinal cord damages myelin, the fatty coating that helps nerve cells send signals. Oligodendrocytes normally build and repair this myelin, but their function can be disrupted in MS, making it harder for the nervous system to replace lost myelin.
Recent research suggests that in MS, some oligodendrocytes may not only struggle to repair myelin but may also take on immune-like roles that could add to ongoing inflammation.
However, most earlier studies only looked at mice with severe experimental autoimmune encephalomyelitis (EAE), a lab-induced disease commonly used to model MS, or at samples from people with late-stage MS. Because of that, it hasn’t been clear when, during the course of MS, oligodendrocytes first begin to malfunction.
“These [prior] studies were conducted with samples from single time points, at the peak of the disease in mouse EAE and from the late stage of disease in human postmortem MS tissue. Thus, the dynamics of [oligodendrocyte dysregulation] throughout the disease process have not been explored,” the scientists wrote.
Tracking oligodendrocyte changes across MS disease stages in mice
To better understand the role of oligodendrocytes, the researchers tracked how these cells changed over time, from the very beginning of disease to late stages, in mice with EAE. They found that some oligodendrocytes developed an “immune-like” pattern of gene activity quite early in disease, right as lesions were beginning to form, and these inflammatory cells stayed active into later stages.
“Our data indicate that the transition of [oligodendrocytes] to immune-like states … occurs at early stages of EAE, when lesions are just starting to develop, and persists at late stages,” the scientists wrote.
The researchers also showed that mature oligodendrocytes do not all respond to disease in the same way. Some subpopulations were more likely to shift into immune-like states, while others were more inclined to support repair. That suggests potential therapies targeting oligodendrocytes may need to be tailored to specific cell subtypes.
Finally, the team found evidence that some oligodendrocytes retain a “memory” of earlier inflammation. These cells held on to molecular marks from that exposure, which the researchers said may make them more likely to stay in an immune-like state instead of returning to a repair-focused profile.
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