The immune system is like a complex defense team, with different types of cells that each play unique roles to keep our bodies safe from harmful invaders like bacteria, viruses, and even cells that might turn cancerous. Each immune cell has its own “job description” and together, they form a well-organized system to recognize, attack, and remember these threats. In MS, this defense system goes awry and mistakenly attacks the body’s own tissues. ACP’s resources facilitate research efforts that explore how this process goes wrong in MS, supporting discoveries that lead to better treatments.
White blood cells, the “soldiers” of the immune system, are divided into various types. T-cells and B-cells are like special agents with their own training. T-cells detect infected cells and help destroy them, while B-cells produce antibodies to recognize and fight off harmful invaders like bacteria, viruses and toxins. Among T-cells, there’s a special group called regulatory T-cells (also known as “Tregs”), which act like “peacekeepers” in the body. They help control and calm down the immune system, making sure it doesn’t accidentally attack healthy cells. In short, Tregs act like the immune system’s brakes, preventing it from causing harm.
Over 20 years ago, investigators at Yale discovered regulatory T cells. These cells were later found to be linked to autoimmune diseases like MS, where improper function may drive disease. Until recently, the mechanism behind this dysfunction hasn’t been clear.
Other immune cells include macrophages and neutrophils, the cleanup crew, which identify and “eat up” harmful particles and dead cells. Natural killer (NK) cells are like surveillance experts, seeking out and attacking cells that don’t look right, such as early cancer cells. Together, these cells create a coordinated response that protects us and even builds “memory” of past infections, making future responses faster and stronger.
Autoimmune diseases like MS are known to be influenced by a mix of genetic and environmental factors. In 2018, the Yale research team discovered that high salt levels contribute to the development of MS. They found that excess salt activates a pathway that disrupts regulatory T cells and triggers inflammation. This effect is driven by a salt-sensitive enzyme, called SGK-1 (Serum/Glucocorticoid Regulated Kinase 1).
SGK1 is an enzyme (a type of protein) that helps the body manage salt, water, and blood pressure, mainly in the kidneys. It also protects cells from damage during stress, injury, or infection, helping them to survive and work properly. In the immune system, SGK-1 helps immune cells respond to stress and communicate effectively to protect the body, either by boosting or calming down immune activity as needed.
A recent Yale-led study shed more light on the dysfunction of regulatory T cells in MS. Researchers used a technique called RNA sequencing to study the activity of genes in people with MS compared to healthy individuals. The researchers found that a gene called PRDM1-S is more active than normal in people with MS. This means that the gene is producing more of its protein, which could affect how the immune system works. Interestingly, increased PRDM1-S activity led to higher levels of the salt-sensitive SGK-1 enzyme (which disrupts the function of regulatory T cells). They also found high levels of PRDM1-S in other autoimmune diseases, suggesting that regulatory T cell dysfunction may be a common thread between them.
The PRDM1-S gene produces a protein that is essential for maintaining a healthy immune response. It plays a key role in regulating the development and function of immune cells, particularly B cells and regulatory T cells. In short, PRDM1-S acts like a “switch,” ensuring immune cells work at the right time and in the right way to protect the body without causing harm.
These findings highlight a promising new target for the universal treatment of autoimmune diseases. The research team, in collaboration with other Yale investigators, is expanding its efforts to develop drugs that reduce PRDM1-S production in regulatory T-cells, aiming to create treatments effective for a range of autoimmune diseases. Driving this type of research forward is central to ACP’s mission, offering hope for transformative therapies that could profoundly impact the lives of those with MS.
