UF Health researchers map early immune attack in Type 1 diabetes

GAINESVILLE, Fla. — A new study by University of Florida Diabetes Institute researchers provides one of the clearest pictures yet of the development of Type 1 diabetes, strengthening understanding of how the autoimmune attack that destroys insulin-producing cells unfolds.

The five-year investigation and analysis of 16 million pancreatic cells using advanced imaging technology helps identify potential new therapeutic targets to alter the disease’s trajectory.

The study is published today in Nature Metabolism with collaborators in Switzerland.

“What I think this paper does is to guide us in identifying the inner pieces of that puzzle of how and why Type 1 diabetes develops,” said Mark Atkinson, Ph.D., a member of the UF Diabetes Institute and the study’s senior author.

“We have, for years, been working with the outer edges and corner pieces of this jigsaw puzzle,” he said. “With this study, we inform the field regarding novel changes that occur in the pancreas, insights that will be helpful for developing potential therapies moving forward.”

In Type 1 diabetes, the immune system mistakenly attacks insulin-producing beta cells.

The study examined donated pancreatic tissue from people at multiple stages of Type 1 diabetes, including some who had not yet developed symptoms.

UF Health researchers observed immune cells gathering near islets — clusters of cells in the pancreas that contain beta cells. When those immune cells moved close to the islets, they changed in ways that signal their activation.

The study suggests that two types of immune cells work in tandem during the early stages of Type 1 diabetes. Macrophages, a type of white blood cell, act like first responders at a fire, but, in this case, erroneously sensing trouble. They call in reinforcements — T cells that carry out the attack on beta cells.

The findings strengthen evidence that this immune attack begins before a person is diagnosed and before symptoms emerge.

The scientists also observed that the beta cells become dysfunctional very early in the disease’s progression.

“What studies like these help us do is improve understanding earlier in the disease process and tailor therapies to stop it,” said study co-author Maigan A. Brusko, an assistant professor in the UF College of Medicine’s Department of Pathology, Immunology and Laboratory Medicine.

The study’s success was enabled by advances in imaging mass cytometry, a technique that provides a much more detailed view of cells than less sophisticated methods. The process allows researchers to tag different cell types in pancreatic tissue and map their distribution and behavior across different disease stages.

“What that allows you to do is understand a lot more because you get much more information about each individual cell,” Brusko said. “Historically, experiments have collected data from three or four protein markers. This technique collects nearly 100 at one time.”

She compared it to a smartphone navigation app that provides drivers with real-time directions using GPS and live traffic information.

“It’s like seeing the other drivers on the road, but also where they’ve been and where they're going,” Brusko said. “You get so much more information about cellular behavior.”

Tissue samples used in the study were obtained from the UF-based Network for Pancreatic Organ donors with Diabetes, or nPOD, the world’s largest repository of such tissue and a major resource for researchers worldwide.

Imaging mass cytometry “provides an unprecedented level of information about what is going on in the human pancreas during diabetes,” said UF Health researcher and study co-author Clive Wasserfall, Ph.D., an assistant professor in the pathology department.

“That tells us information we did not have access to before,” he added. “And that leads to new ways of thinking about therapies. Using human tissue from nPOD research is truly changing our views on how Type 1 diabetes develops. I am optimistic that today’s discoveries will lead to tomorrow’s therapeutic innovations.”