medicine.washu.edu
In recent research, scientists at Washington University School of Medicine in St. Louis have discovered how the brain naturally protects itself from harmful immune responses. This mechanism, involving “guardian peptides” – specific protein fragments that appear to regulate immune activity – shows potential for therapeutic application in diseases such as multiple sclerosis (MS). In mouse models of MS, the depletion of these peptides increased vulnerability to immune attacks, while replenishing them helped mitigate symptoms. The study’s findings, published in Nature, suggest new avenues for therapies targeting neuroinflammatory conditions.
This study suggests that the brain continuously interacts with the immune system to maintain what is known as “immune privilege,” a state that prevents excessive immune responses within the central nervous system (CNS). Researchers found that the brain and spinal cord produce guardian peptides that engage with immune cells at the CNS borders. In healthy brains, these peptides interact with specific immune T cells, encouraging a regulatory effect that suppresses potentially harmful immune responses. In mice with MS, however, the researchers found these peptides were significantly depleted, leading to immune attacks on myelin, the protective covering on neurons.
“We have found guardian brain peptides that actively engage with the immune system to keep it in check, possibly preventing destructive immune responses,” said Jonathan Kipnis, PhD, of Washington University School of Medicine. Kipnis noted that these peptides may help maintain the brain’s immune privilege and could serve as the basis for new therapies designed to control inappropriate immune responses in neuroinflammatory diseases.
To test potential applications, researchers administered vesicles containing brain-derived peptides directly into the cerebrospinal fluid of mice with MS. This treatment activated regulatory T cells, which play a role in dampening excessive immune activity. Mice that received the peptide treatment showed improvements in motor function and reduced disease progression compared to those given a control treatment, suggesting that replenishing these peptides may restore immune balance in the CNS.
Min Woo Kim, a researcher involved in the study, explained that this “novel process in the brain” involves actively presenting a “healthy image” of itself to the immune system. In MS-affected mice, this image appears altered, pointing to the potential for these protein signatures to serve as early markers for MS and possibly other neuroinflammatory and neurodegenerative diseases.
The findings highlight a promising new approach for treating neuroinflammatory diseases. By leveraging naturally occurring peptides that regulate immune responses within the CNS, researchers hope to develop therapies that reduce damaging inflammation without suppressing the immune system entirely. Such a strategy could be particularly impactful for conditions like MS, where autoimmune attacks on the myelin sheath lead to progressive disability.
The research also underscores the significance of brain-immune communication in disease prevention and opens avenues for exploring whether similar peptide markers could be relevant in other conditions, including Alzheimer’s disease. Future studies may reveal additional applications for these brain-derived peptides in diagnostics and treatments for CNS disorders.