Researchers have discovered a mechanism through which the brain protects itself from immune system attacks. In a study involving mice with multiple sclerosis, it was observed that specific ‘guardian’ proteins, which help train the immune system, were significantly reduced. However, restoring these proteins led to improvements in symptoms.
The brain is in constant communication with the immune system, striving to maintain a careful balance between protecting against damage and infection while safeguarding healthy tissues.
Scientists from Washington University School of Medicine in St. Louis have uncovered how the brain and immune system maintain this balance. Their research identified segments of immune-boosting proteins, known as guardian peptides, that are created in the brain and spinal cord. These peptides help regulate the brain’s immune response while facilitating healthy communication with the immune system.
Published on October 30 in the journal Nature, this study may lead to advancements in treating conditions like multiple sclerosis (MS) and Alzheimer’s disease, along with others.
“We have identified guardian brain peptides that interact with the immune system to help regulate its activity, potentially preventing harmful immune responses,” stated Jonathan Kipnis, PhD, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology & Immunology and a BJC Investigator at WashU Medicine. “These peptides may support the immune system in maintaining a state of ‘immune privilege.’ We are excited about the prospect of developing these proteins from healthy brains into therapies that could inhibit inappropriate immune responses and contribute to better disease-modifying treatments for neuroinflammatory conditions.”
Immune surveillance involves a particular group of T cells that can trigger a response when alerted to a potential threat. Such alerts are conveyed through tiny protein fragments displayed on the surfaces of other immune cells. If T cells perceive these fragments as a danger, they initiate an attack.
The team found that guardian peptides were presented by immune cells located at the brain’s borders, where they attracted and activated a specific type of T cell designed to regulate the immune response, thereby reducing abnormal reactions.
Min Woo Kim, a graduate student in WashU Medicine’s Medical Scientist Training Program and a member of the Kipnis lab, studied presenting immune cells from the brains of healthy mice and their associated immune tissues. He discovered an abundance of brain proteins presented by these cells, with the predominant protein being a component of myelin sheath, which protects neurons and is damaged in MS.
The study also revealed that these proteins were significantly lacking in mice with MS. By administering the missing brain-derived peptides through vesicles—small membrane-bound compartments—into the cerebrospinal fluid of these mice, researchers found that this therapy activated and increased a specific group of suppressor T cells. As a result, motor function improved, and the progression of the disease was slowed down in treated mice compared to those receiving standard vesicles.
“We have discovered a unique process where the brain actively interacts with the immune system to project a healthy image of itself,” remarked Kim. “This image is altered in mice with multiple sclerosis. We believe that other neuroinflammatory and possibly neurodegenerative diseases might exhibit distinct protein signatures to the immune system, raising the exciting possibility of utilizing these signatures for early diagnosis.”
Collaborators from WashU Medicine who contributed to the study include Cheryl Lichti, PhD, an associate professor of pathology & immunology; Clair Crewe, PhD, an assistant professor of cell biology & physiology; Maxim N. Artyomov, PhD, the Alumni Endowed Professor of Pathology & Immunology; and the late Emil R. Unanue, PhD, who passed away before the study’s completion. Unanue was recognized with the Albert Lasker Basic Medical Research Award in 1995 and was a pioneer in exploring the interactions between T cells and presenting cells, enabling the former to detect and respond to external invaders.
