A long-observed phenomenon-the reduction of multiple sclerosis (MS) relapse rates during pregnancy-has yielded a key insight into the body’s immune regulation, according to new research from the University Hospital Hamburg-Eppendorf.Scientists have identified a brain-controlled signaling pathway involving the messenger substance GDF-15, perhaps paving the way for novel MS therapies. The findings,published today in *Nature Immunology*,offer a deeper understanding of how the central nervous system interacts with the immune system in MS,a disease affecting more than 2.8 million people worldwide[[1]].
Women with multiple sclerosis (MS) may experience an 80% reduction in relapse rates during pregnancy, and researchers have now pinpointed a key mechanism behind this phenomenon. Scientists at the University Hospital Hamburg-Eppendorf (UKE) have discovered that the brain actively controls and regulates inflammation and the immune system, offering new insights into potential MS therapies.
Reading time: 2 minutes
“Our goal was to understand how pregnancy regulates the increased inflammatory activity in MS. We were able to show for the first time that the brain actively monitors the state of the immune system and can intervene to regulate it. This newly identified signaling pathway opens up promising approaches for new MS therapies,” explained Manuel Friese, Director of the Institute for Neuroimmunology and Multiple Sclerosis at UKE, who led the research published in Nature Immunology. This discovery is significant because MS is a chronic neurological disease affecting millions worldwide.
In MS, misguided immune cells enter the brain and spinal cord, causing inflammation and damaging nerve cells by breaking down the protective layers around nerve fibers. Over time, this leads to increasing neurological impairment.
Immune System Suppressed During Pregnancy
The reduction in inflammatory activity during pregnancy has long been observed. To protect the developing fetus, the immune system of pregnant women is naturally suppressed, and this effect can positively influence inflammatory conditions like MS. According to the new findings, a crucial role is played by the immunosuppressive messenger substance GDF-15 (Growth/differentiation factor-15), released by the fetus, a recent press release from the Hamburg University Hospital stated.
GDF-15 Reduces Inflammation Through Brainstem Cells
Elevated levels of this immunosuppressive messenger are also found in individuals with MS, suggesting the body attempts to limit inflammation on its own. However, researchers were surprised to find that the receptor for GDF-15 is present only on nerve cells in the brainstem, not on immune cells themselves.
The international research team found that these specific GDF-15-sensitive nerve cells in the brainstem are connected to the sympathetic nervous system – a part of the autonomic nervous system that prepares the body for stress, danger, or exertion. When this signaling pathway is activated, immune organs like the spleen release more of the neurotransmitter norepinephrine. This inhibits the activation of pro-inflammatory immune cells and prevents their migration into the central nervous system – the brain and spinal cord.
Potential Target for Future MS Treatments
Notably, this immunosuppressive effect is triggered by a very small group of nerve cells. “Although these nerve cells are present in only small numbers, they can suppress the immune response so strongly that no inflammatory cells enter the brain and spinal cord,” said Jana Sonner, the study’s first author.
Because these crucial nerve cells in the brainstem lie outside the blood-brain barrier, the signaling pathway is particularly accessible for therapeutic interventions. Many drugs with potential effects on the central nervous system fail because they cannot cross this protective barrier.
In a preclinical mouse model, the research team successfully enhanced this MS protective mechanism through both gene therapy and administration of recombinant GDF-15. In both cases, disease activity was significantly reduced or even prevented.
Approximately 13,500 people in Austria are affected by MS. It is the most common neurological disease among young adults, with the peak age for diagnosis between 20 and 40 years old. Two-thirds of people with MS are women. Significant progress has been made in treating the most common form, relapsing-remitting MS, over the past 25 years, with medications effectively reducing relapse rates and slowing disease progression.
(Source: SN, APA)
