Type 1 diabetes is an autoimmune condition in which the body’s immune system mistakenly targets the cells that produce insulin, the hormone essential for regulating blood sugar. Researchers at Scripps Research have identified a previously unknown cell type that aids in safeguarding insulin production, pointing to new strategies for stopping or reversing the disease.
The study, published in Cell Reports, shows that vascular‑associated fibroblastic cells (VAFs) act as molecular peacekeepers within the pancreas, actively shielding insulin‑producing cells from immune attack.
These findings clarify several perplexing aspects of type 1 diabetes, such as its long preclinical phase—where immune-mediated destruction of pancreatic cells begins while blood glucose remains normal—and suggest that early therapeutic intervention might be achievable.
Luc Teyton, professor of Immunology and Microbiology at Scripps Research and senior author, remarks, “Identifying VAFs is an exciting step toward understanding how the pancreas negotiates with the immune system.”
He adds, “This discovery unlocks a new perspective on autoimmunity and could guide the development of better treatments for type 1 diabetes, as well as preventive and reversal strategies.”
For the 1.6 million Americans living with type 1 diabetes, daily management involves frequent insulin injections, continuous glucose monitoring, and strict dietary control; lapses can lead to life‑threatening complications.
To locate VAFs, Teyton’s team took an unconventional route focused on the pancreas’s own physiology and disease states. They honed in on the post‑capillary venules, a site that often triggers inflammation, and combined advanced imaging, cell‑labeling and single‑cell analysis to examine how a healthy pancreas keeps inflammation in check.
They employed a cell‑labeling technique called FucoID, created by professor Peng Wu, which allowed rapid identification and isolation of target cells.
Results revealed that VAFs possess a range of specialized functions that prevent autoimmunity against insulin cells. Immune cells rely on antigen presentation—displaying protein fragments to trigger responses—and VAFs contribute by presenting pancreatic peptides while also sending signals that calm the immune system and induce a tolerant state known as anergy.
The pancreas faces distinct immunological challenges as part of the digestive system, constantly exposed to potential inflammatory triggers from food and the environment.
Teyton’s work shows that ongoing inflammation—whether from infection, toxins or other causes—can overwhelm VAFs, provoking immune activation and leading to type 1 diabetes. Once overwhelmed, autoimmunity spreads in the pancreas, destroying the insulin‑producing cells that maintain blood glucose balance.
Don Clarke, first author and former postdoctoral researcher, comments, “This discovery reframes how we think about type 1 diabetes. Instead of asking why the immune system attacks, we can now ask what disrupts the pancreas’s natural tolerance and how we can restore it.”
The protective role of VAFs opens a new research avenue focused on enhancing the body’s own tolerance mechanisms. The group envisions therapies that reinforce VAF functions—such as boosting anergy states—and anti‑inflammatory treatments to shield these cellular peacekeepers from overwhelming inflammation.
These findings also have broader relevance to other autoimmune conditions and organ transplantation, where similar tolerance mechanisms may operate.
Moving forward, the team aims to translate laboratory discoveries into clinical applications, pursuing personalized treatments that cooperate with the body’s natural defenses rather than blunt the immune system, thereby improving outcomes for millions at risk for type 1 diabetes.
In partnership with Scripps Research Assistant Professor Joseph Jardine, the researchers continue to investigate VAFs as pancreatic peacekeepers and to develop strategies that strengthen or restore their protective functions when faced with excessive inflammation. This approach could enable prevention of type 1 diabetes by reinforcing the body’s inherent tolerance.