UF Health study maps hidden immune signals in Type 1 diabetes

GAINESVILLE, Fla. — Type 1 diabetes researchers have made great progress in understanding the disease in the last two decades, even as a cure remains elusive.

Now they have something that benefits any scientific effort.

It’s a map.

University of Florida Health scientists have created one of the most detailed maps yet of gene activity in the pancreas of people with Type 1 diabetes. The map shows which genes are turned on, or expressed, and where they are active within the organ, helping researchers pinpoint the biological signals driving the disease.

By revealing those signals, the work highlights potential targets for new drugs to slow the disease or, perhaps one day, stop it altogether.

Researchers published their findings in Cell Reports on Tuesday.

“You’re looking at a map, almost like a topographical map of an organ or tissue and saying, in this particular ZIP code or region, these are the genes that are highly expressed,” said the study’s senior author, Todd Brusko, Ph.D., director of the UF Diabetes Institute and a leading diabetes researcher.

Brusko is a professor in the UF College of Medicine’s Department of Pathology, Immunology and Laboratory Medicine.

An expressed gene has been switched on, allowing the cell to use its instructions to perform a function.

Scientists in the study used a method called spatial transcriptomics to place thin tissue slices on slides that capture genetic material from thousands of tiny spots. They then sequence the captured genetic material to identify which genes are turned on at each location.

Older methods for examining an organ like the pancreas would break up tissue and study cells individually. That, however, does not show where those cells are located.

Researchers mapped gene activity across the pancreas tissue from four groups of people. They included people without diabetes, individuals with one diabetes-related autoantibody, those with multiple diabetes-related autoantibodies and patients with Type 1 diabetes.

Antibodies are proteins produced by the immune system that recognize and tag harmful invaders, such as viruses, for destruction. Autoantibodies are antibodies that mistakenly target the body’s own proteins instead of harmful invaders. Their presence indicates someone is at high risk of Type 1 diabetes even if they have no symptoms.

Scientists aimed to examine the disease at several stages — from healthy tissue to early immune warning signs and, finally, to established diabetes. By comparing these stages, researchers could see how gene activity changes as the disease develops.

That is valuable information for a scientist investigating what triggers Type 1 diabetes, an autoimmune disease in which the body’s immune system mistakenly attacks and destroys the cells in the pancreas that make insulin.

The maps showed increased activity of a gene linked to inflammation. That signal was unusually strong in the pancreas and nearby lymph nodes of people with Type 1 diabetes. Inflammation produced by the autoimmune attack is believed to contribute to the disease. That finding may point to a potential target for future treatments.

For decades, scientists have tested drugs developed for other autoimmune diseases, like rheumatoid arthritis, and hoped they might also work in Type 1 diabetes. The new gene map offers a more direct strategy for developing drugs to treat the disease.

“This really allows us to look in the target organ and identify the pathways that are active in people who develop disease,” Brusko said. “Now with the ability to look in the target organ itself, we can really have a good idea of whether a drug therapy is going to be effective.”

The research relied on donated organs collected through the National Institutes of Health-supported Human Pancreas Analysis Program and the UF-based Network for Pancreatic Organ donors with Diabetes, or nPOD. nPOD is the world’s largest repository of Type 1 diabetes pancreatic tissue.