When the researchers turned off the Clec16a gene in diabetes-prone mice, most of the animals did not develop the disease.
When the study team, including Stephan Kissler, assistant professor of medicine at Harvard Medical School, Boston, MA, turned the gene off in mice genetically engineered to develop diabetes, the vast majority of the animals did not develop the disease.
The researchers believe the discovery brings closer the day when we will be able to prevent diabetes.
They report their findings in the journal Immunity.
Prof. Kissler, an immunology investigator at Harvard's Joslin Diabetes Center, says they think the reason Clec16a is associated with so many different types of autoimmune disease is because it plays a key role in a process at the heart of the immune system. He explains:
Clec16a is involved in the development of type 1 diabetes through autophagy
Autophagy is a process that goes on in all cells. Literally it means "eat oneself," and is the process through which cells digest their own waste proteins and put the recycled material on their cell surfaces - like putting out the trash.
Autophagy can be activated for different reasons. For instance, if there is a shortage of nutrients or if cells are infected with a virus.
However, epithelial cells in the thymus - a specialized immune system organ that resides behind the breastbone and above the heart - use autophagy in a different way. They use it to show T cells which proteins belong in the body and which should be eliminated.
The researchers showed that the Clec16a gene is involved in the development of type 1 diabetes through the process of autophagy.
Prof. Kissler explains:
"By changing autophagy in TECs [thymic epithelial cells] you change T cell selection, and by changing T cell selection you change the risk of autoimmune disease."
Switching Clec16a off in diabetes-prone mice significantly reduced risk of disease
For their study, he and his colleagues turned the gene off in 40 mice engineered to develop type 1 diabetes. Only 2 mice developed diabetes compared to 60% in another group of similar mice that were left to develop naturally.
While the team could see that switching off Clec16a made a big difference, they could not see which organ was involved or how the effect came about.
Through a series of transplant experiments, they found that the gene regulates T cell education indirectly in the thymus.
The team has achieved similar results with other genes before, but nothing as dramatic as with Clec16a, says Prof. Kissler.
In a further investigation, the team found that Clec16a is also involved in of human cell autophagy.
They now plan to find out if Clec16a affects T cell education in the human thymus. Prof. Kissler concludes:
"All we know for now is the gene has an effect on human autophagy. Is the same true in human thymus? How does that compare to what we've described in the mouse?"
Discovering that Clec16a plays the same role in the human thymus as in the mouse, would be a big step toward solving the mystery of how a complicated diseases like type 1 diabetes, multiple sclerosis and other autoimmune disorders develop.
Earlier this year, Medical News Today learned of another study that found women with multiple sclerosis may have a lower intake of anti-inflammatory and antioxidant nutrients, such as folate, vitamin E and magnesium. However, the researchers could not say if this is a cause or an effect of the disease.