For the first time, researchers have revealed that during the development of Type 1 diabetes (T1D), when insulin-producing cells in the pancreas are under attack from T lymphocytes, the cells lining the pancreatic duct reprogram themselves in an attempt to suppress autoimmune T cell responses. This study is published in Nature Metabolism.

“The first events that occur in a patient heading towards Type 1 diabetes, the events that trigger autoimmunity, have been difficult for researchers to pin down because of our inability to biopsy the pancreas, and the fact that clinical diagnosis is only made once massive beta cell destruction has occurred,” says senior author Golnaz Vahedi, an associate professor of genetics and member of the Institute for Diabetes, Obesity and Metabolism at the Perelman School of Medicine. “That is why it is so important to develop a better understanding of the earliest molecular events in T1D pathogenesis, so we can uncover more about biomarker identification and disease prevention.”

Autoimmune diseases, which affect as many as 23.5 million Americans, occur when the body’s immune system attacks and destroys healthy organs, tissues and cells. There are more than 80 types of autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease, and T1D. In T1D, immune cells called T lymphocytes attack and destroy insulin-secreting pancreatic beta cells and the pancreas stops producing insulin, the hormone that controls blood sugar levels.

“Although it might be an ultimately unsuccessful attempt of the pancreas to limit the adaptive T cell response responsible for destroying beta cells, this finding that the ductal cells are capable of playing this suppressive role towards autoimmune T cell responses is unprecedented,” says co-senior author Klaus Kaestner, the Thomas and Evelyn Suor Butterworth Professor in Genetics. “Our study shows that these cells, which had never previously been linked to immunity, may change themselves to protect the pancreas.”

The research was funded by grants through the National Institutes of Health.