cells under influence
A group of scientists led by Prof. Yaron Cohen from the Department of Immunology at the Weizmann Institute of Science succeeded in discovering the molecular mechanism of a therapeutic vaccine that may be used to treat the development of type 1 diabetes. Deciphering the mechanism may increase the overall effectiveness of the vaccine, which is currently being tested in advanced clinical trials.
Type 1 diabetes is an autoimmune disease caused when the immune system attacks and destroys the insulin-producing beta cells in the pancreas. This destruction causes a lack of insulin, which is necessary for the body to assimilate sugars into the body's cells that convert them into energy.
Prof. Cohen and his research partners previously developed a therapeutic vaccine that blocks the development of autoimmune diabetes in laboratory animals. They discovered that a certain protein, called HSP60, or even a small part of the protein, the peptide p277, is able to block the autoimmune response that causes the disease. The vaccine is currently being tested in clinical trials in Europe and the US, but the exact mechanism of its effect was not known until now.
"In the past, we knew that this protein could bring about a change in the activity of the immune system and moderate its activity, but we did not know how exactly it does this," says Prof. Cohen. Now the scientists were able to precisely identify the immune cells that p277 affects and the mechanism of its action. These findings were published in the scientific journal Journal of Clinical Investigation.
Autoimmune diseases occur when certain T cells of the immune system attack the body's own cells and tissues. The scientists were able to discover that p277 directs the activity of the immune system in two ways. It turns out that the peptide stimulates the activity of a certain type of T cells, which regulate the system. In addition to this, the regulatory T cells treated with p277 cause the T cells that attack the body's own tissues to secrete anti-inflammatory substances, instead of the inflammatory substances they secrete in the process in which they cause the auto-immune disease to occur. This dual activity of the peptide further weakens the immune response.
The scientists also showed that to trigger these responses, p277 must activate a receptor called TLR-2 displayed on the membranes of regulatory T cells.
"Understanding the mechanism of p277's activity may allow us to develop ways to mimic the natural regulatory mechanisms, and in this way better control the reactions of the immune system, and avoid the destruction of the insulin-producing cells in the pancreas," says Prof. Cohen.
The post-doctoral researcher Dr. Alexandra Zanin-Zhurov led the project that was conducted in Prof. Cohen's laboratory. The late Prof. Ofer Lider, Dr. Liora Kahlon, the post-doctoral researcher Dr. Guy Tal, and Ra'an Margalit also participated in the research.
