Scripps Research professor wins $3.2 million grant to unlock secrets of type 1 diabetes

Luc Teyton, a professor in the Department of Immunology and Microbiology at Scripps Research, has received a five-year, $3.2 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to help answer the question of how type 1 diabetes manifests and develop potential drugs to reverse or prevent the disease.

Type 1 diabetes is autoimmune disease in which the immune system mistakenly attacks cells that produce insulin, a key hormone that regulates blood sugar levels in the body. About 1.6 million Americans live with type 1 diabetes, and although genetics play a large role in susceptibility, scientists still don’t fully understand what initiates the autoimmune attack.

Working with assistant professor Joseph Jardine, Teyton aims to understand how type 1 diabetes occurs by studying vascular-associated fibroblastic (VAF) cells. Although VAFs are rare, they act as molecular peacekeepers in the pancreas, actively protecting insulin-producing cells from the immune system. Early research by Teyton and his lab suggests that type 1 diabetes may manifest when VAFs become overwhelmed, forcing the immune system to activate and destroy the precious insulin-producing cells that balance blood sugar levels in the body.

Type 1 diabetes significantly impacts the lives of patients and their families, and despite decades of efforts to understand it, the inner workings of the disease remain a mystery. The discovery of VAF is just the tip of the iceberg. In the next phase of our research, we will use this funding to further investigate how we can strengthen these cells in the face inflammation-potentially finding a way to cure.

Luc Teyton, Professor, Department of Immunology and Microbiology, Scripps Research

Teyton’s grant builds on a discovery his team published in September 2025. Working in both mouse models and human pancreatic tissue, researchers identified VAFs clustered around insulin-producing areas of the pancreas. These cells did something unexpected: they presented the pancreas antigens-protein fragments -to the immune system.

Under normal circumstances, only specialized immune cells have the molecular machinery to present antigens that alert the immune system to potential threats. Surprisingly, VAFs also express these molecules and present pancreatic components to passing immune cells. However, VAFs simultaneously express PD-L1, a molecule that provides inhibitory “don’t attack” signals, creating a protective, balanced environment. When persistent inflammation occurs, VAFs dramatically increase antigen presentation while their protective inhibitory signals remain constant. This imbalance – increased alarm signals without proportional, “all clear” signals – can inadvertently trigger the immune system to activate and destroy insulin-producing cells.

The discovery challenged the conventional view of type 1 diabetes. Scientists had long assumed that the disease began when immune cells penetrated the pancreatic islets – clusters containing insulin-producing cells – and directly attacked them. But when Teyton’s team examined tissue from mice and humans, they found that immune cells clustered only outside the islands, not inside them. VAFs are located exactly on this border, between the pancreatic islets and blood vessels.

“We were looking in the wrong place,” adds Teyton. “For years, we assumed that type 1 diabetes began in the pancreatic islets. But our research suggests that the real action happens outside the cells, which should not present pancreatic antigens to the immune system at all.”

Now, a new NIDDK grant will enable Teyton’s lab to explore these findings in greater depth. The team will perform a comprehensive analysis of all antigen-presenting cells in healthy and pre-diabetic pancreatic islets. Using advanced techniques, they will track changes in cell populations as the disease progresses.

The team will also investigate why VAFs only present peptide fragments, rather than traditional antigen-presenting immune cells that present whole proteins. A better understanding of this process may reveal specific goals for therapeutic intervention.

It is also crucial to discover how inflammation interferes with the healthy functioning of the pancreas. Although inflammatory molecules have long been known to induce antigen presentation, recent evidence points to alternative pathways involving diet and gut-derived factors. Scientists will test different inflammatory signals in mice to understand what causes VAFs to turn from protective peacekeepers to potential troublemakers.

“We hypothesize that communication between the gut and pancreas may cause local inflammation that overwhelms the VAF,” Teyton says. “Understanding these factors can reveal entirely new points of intervention.”