The board game Mouse Trap is a Rube Goldberg''s interacting part. Only instead of a falling ball causing a tiny diver to leap into a tubwhich, in turn, springs a trap on some plastic miceproteins trigger other proteins to activate immune cells and direct them toward germs. However, autoimmune illnesses - like multiple sclerosis - can arise.
A new study led by aKelly Monaghana researcher with theWest Virginia UniversitySchool of Medicine suggests that a portion of the Rube Goldberg immune system is regarded as a feasible strategy for MS therapies.
Whenever you have any type of central nervous system problems, you must follow a series of steps to get cells into the brain or spinal cord, according to Monaghan, a doctoral candidate in theDepartment of Microbiology, Immunology, and Cell Biology. Acknowledgement of those immune mechanisms associated with MS can help in developing new therapies.
Her findings appeared in theProceedings of the National Academy of Science.
STAT5, one of the many proteins that circulate in the body that can metaphorically turn genes on or off, has been funded by the National Institutes of Health.
STAT5 is a transcription factor, according to Monaghan. It is a member of the STAT protein family, and it has a tlethora of roles in cell proliferation and inflammation. Importantly, STAT5 proteins must form dimers to regulate gene expression. Tetramers are required to regulate an independent set of target genes.
Monaghan and her colleagues wanted to know if STAT5 tetramers played a role in signaling white blood cells to interact and move through the meninges. If they did play this role, they wanted to know more.
The meninges, if you dont know, are a series of three membranes that surround the central nervous system, she said. They act as a measure of checkpoint, if you desire, to control the migration of cells into the actual brain or spinal cord.
Multiple sclerosis is characterized by the infiltration of immune cells into the meninges.
Monaghan wanted to investigate the molecular chain of events that might result in the STAT5 tetramers being ordered to command another protein called CCL17, to instruct T cells, a type of white blood cell, to attack the central nervous system through a friendly fire.
To investigate this topic, Monaghan and her team used two groups of mice. The first group had been genetically modified so that its STAT5 tetramer proteins could not rearrange themselves in ways that would result in the problematic CCL17 response. The second group was genetically normal.
Both groups of mice were fed with myelin-reactive T cells to form an experimental form of MS, called experimental autoimmune encephalomyelitis (EAE).
In response, genetically-normal mice developed EAE in the conventional way, but genetically modified mice did not. Interrupting their STAT5 tetramer chain reaction protected them against the disease.
Monaghan said the disease was largely ablated, but it was significantly reduced in severity. CCL17 is the pathogenic protein that acts downstream of STAT5 tetramers, according to Monaghan.
Although genetically modified mice exhibit milder and long-term paralysis, a later examination of their spinal cords revealed healthier nerves that are better at transducing signals.
MS is extremely complicated, according to Monaghan. We found that the complex immune interactions between the cells are really what drives the difficulty in understanding this disease.
According to the National Multiple Sclerosis Society, insights similar to those obtained from this study can lead to future treatments for MS.
Patients with MS may experience a lifetime, but their clinical symptoms are worse when the disease progresses, according to Edwin Wan, a Monaghans mentor and assistant professor. Some MS treatments have demonstrated a well-known technique that may reduce symptoms, but they are not able to stop disease progression. We do not have a complete picture of how the disease is initiated and progresses.
The findings of these research help to clear the gap between the two, bringing hypothetical MS therapies closer to reality.
These findings are likely to have much greater implications to other autoimmune illnesses, according to Monaghan, because there may be several other autoimmune illnesses that are regulated by STAT5 tetramers and the downstream signaling pathway, which is quite helpful.