A lot of different immune cells play a role in causing type 1 diabetes. Stephan Kissler, Ph.D., Investigator in the Section on Immunobiology at Joslin Diabetes Center, is trying to understand the genetics behind what turns these immune cells against the body.
You probably have heard of T cells. But did you know there are many different kinds? There are memory T cells, suppressor T cells, helper T cells and more. Branching out from the T cells, there are other lettered immune cells that play a role, including B cells (not to be confused with beta cells, which are marked with a β rather than a B). B cells produce antibodies, which are the parts of the immune system that try to get rid of bad things in your body. In the case of type 1 diabetes, some antibodies falsely identify beta cells as a threat.
In a new study published in Genes and Immunity, Dr. Kissler has found a relationship between a gene called RGS1 and the helper form of T cells that interact with B cells. Helper T cells recognize a foreign element such as a virus or—in the case of type 1 diabetes—beta cells. They then alert B cells to produce antibodies to target what they’ve discovered.
This interaction happens in lymph nodes and the spleen. The recent findings from Dr. Kissler’s lab show that turning off the RGS1 gene changes the way T cells interact with the B cells. The fewer interactions between helper T cells and B cells, the less likely the B cells are to produce antibodies targeting beta cells.
“The RGS1 gene is important to allow activated T cells to move into the regions with all the B cells, where they help the B cells get activated and produce antibodies,” Dr. Kissler explains. “These are the T follicular helper cells. If you don’t have any of these cells, the antibody production doesn’t work anymore.”
This study was built off of research done in other labs that showed that T follicular helper cells are found to be increased in the blood of people with T1D. This research was done in mouse models, and stopping the action of RGS1 didn’t reduce the incidence of type 1 diabetes. This wasn’t altogether surprising, though. There are so many genes associated with type 1 diabetes that it’s unlikely modifying one alone would have an effect. The more autoimmune-related genes the researchers understand the function of, however, the better they are equipped to creating a medication that can target a key mechanism involved in disease and hopefully stop autoimmunity.
The main benefit of this study has been a deepening of our understanding about how autoimmunity works, and not just in type 1 diabetes. Many of the genes responsible for the immune attack in diabetes are the same ones that play a role in other autoimmune diseases such as Multiple Sclerosis and Rheumatoid arthritis.
“We’re continuing to test a number of other genes to see if one strikes us as being a very potent modifier of type 1 diabetes,” he adds. ““The more pieces of this puzzle we can lay down, the better a picture we have to figure out the best ways to intervene in the disease. And this piece of information about RGS1 might become valuable down the line when we know more about other genes, because it might fall into place in the puzzle.”