Multiple sclerosis (MS) is an autoimmune disease that affects millions of people across the United States. It has a predilection for younger women and usually first causes symptoms in the third or fourth decade of life. Symptoms vary and can be as subtle as fatigue or more obvious such as numbness or loss of vision.
Most diagnosed with the disease have symptoms that come and go over time. This version of the disease is called “relapsing-remitting” MS and is the less severe form. Over time, attacks can get worse and closer together with shorter normal periods in between. Treatment for these individuals aims at trying to keep relapses far apart while preventing symptom progression when they occur.
The more severe form of the disease is called “primary progressive” MS. Those with this diagnosis don’t have normal periods in between attacks and their symptoms progress over time to cause permanent, worsening neurologic dysfunction.
Unfortunately, little is understood about what exactly causes a person’s immune system to start attacking the nerve cells of the body in MS. Research is ongoing as to whether viral infection might play a role and how sun exposure and vitamin D might fit in, but new research out this week has found a new group of immune cells that play a key role in setting off the reaction.
There are many different defenders of the body in the immune system. Some immune cells work together against a common enemy, while others target only a few specific kinds of invaders. One group of defenders is the T helper cells. In many ways, their name describes exactly what they do. These cells find invaders with proteins that match their receptors and fire out a warning flare that draws closer cells that can respond with deadly force.
This flare often comes in the form of a hormone, a chemical signal that circulates in the blood as a message to other cells able to read it. The researchers used a mouse model of MS to try and get a better understanding of exactly how this signaling plays a role in MS. They focused in on a set of signal proteins called STAT5 known to be involved in responding to immune hormone signals, but that hadn’t been studied in autoimmune disease.
To figure out if STAT5 was important in MS, the researchers blocked the gene in a group of MS mice and looked to see how their immune cells would behave. Interestingly, these mice were much less likely to get MS. The team thought that maybe this change was because the immune cells involved couldn’t get to the brain anymore, but when they looked they found the cells present in the brain. What they saw instead was lower numbers of these cells, indicating that even though the immune system could still access the brain, it wasn’t causing the inflammation that leads to MS.
On further investigation, the researchers found that a specific group of previously unknown T Helper cells was playing a role. They called these cells TH-GM after the inflammatory immune hormone GM-CSF that they release. It seemed that STAT5 played a key role in allowing these cells to release GM-CSF in the brain, which then led to the inflammation that triggered MS.
But what was flipping the STAT5 switch that led to this whole situation in the first place? After some searching, the research team found that another hormone, called IL-7 involved in many aspects of immune system function, was the trigger.
While the research took place in mice, the authors of the study are looking to move into humans to see if these TH-GM cells are present and what role they’re playing in autoimmune diseases. If the situation proves similar in humans, new medications aimed at blocking the activity of IL-7 and STAT5 might appear to help stop the damaging inflammation that causes so much suffering in MS.