In some patients, the repair process managed by the immune system is lacking, which explains why their pathology evolves more quickly.
In patients with multiple sclerosis, the immune system is both the poison and the cure, according to a study published in the journal Brain. This work, carried out by Inserm researchers, sheds light on why this pathology progresses more slowly in certain patients.
Multiple sclerosis is an autoimmune disease. T cells, a special type of white blood cell, attack the brain and spinal cord by destroying the myelin sheaths that surround and protect neurons. Paradoxically, these immune cells are also responsible for repairing this damage. They activate other white blood cells, called macrophages and microglia, which are responsible for attracting stem cells to the injury site in order to rebuild the myelin sheath. Thus, “the ability to repair myelin efficiently is a key factor in countering the progression of the disease,” notes Inserm.
However, studies have shown that this phenomenon of myelin regeneration could be lacking. While lesions can be completely repaired in some patients, they may persist in others. A difference which suggests that the action of the immune system is a highly regulated phenomenon.
Stem cells do not differentiate
To better understand these mechanisms, the researchers injected mice with spinal cord damage with lymphocytes from healthy people and patients with multiple sclerosis. They were then able to find out where the problem was.
According to their observations, lymphocytes manage to recruit macrophages and microglia at damaged neurons. On the other hand, it is at the next stage that things get stuck: the microglia cannot induce the differentiation of stem cells in patients with “a low capacity for remyelination”. While in patients with a strong regenerative capacity, the transformation of stem cells goes to the end.
By comparing the molecules secreted by T lymphocytes, the scientists discovered 3 substances associated with good remyelination and 3 other proteins linked to a poor repair process. Inhibiting these last 3 molecules could make it possible to activate macrophages and microglia and thus slow the progression of the disease, say the authors.
Therapeutic track
“The study of lymphocytes from patients with strong remyelination capacities is a promising avenue for developing new myelin regeneration strategies,” explains Violetta Zujovic, researcher at Inserm and main author of this work. In addition, the systematic study of their lymphocytes would make it possible to offer assistance in diagnosis and treatment, and to develop precision medicine adapted to each patient “
The authors also indicate that these results could provide answers, or even pave the way for new therapeutic avenues, for Alzheimer’s disease or Parkinson’s disease.
.
