Uncovering a Cellular Peacekeeper in the Pancreas
Researchers at Scripps Research have identified a novel cell type that actively protects insulin-producing cells from autoimmune attack. The discovery centers on vascular-associated fibroblastic cells (VAFs), which appear to act as molecular peacekeepers within the pancreas. Published in Cell Reports on September 23, 2025, the study offers a potential new avenue for preventing or reversing Type 1 diabetes by preserving the body’s own insulin-producing capacity.
What Are VAFs and Why Do They Matter?
VAFs sit at the crossroads of the pancreas’ immune environment and its endocrine function. The team led by Luc Teyton examined how these fibroblastic cells participate in antigen presentation and immune signaling. In healthy tissue, VAFs help display pancreatic protein fragments to the immune system while simultaneously sending signals that push immune cells toward a tolerant, non-destructive state known as anergy. This balancing act can prevent autoimmune destruction of insulin-producing beta cells.
The Mechanism: Tolerance Over Turmoil
Key to the discovery was tracing how immune cells patrol the body and decide whether to mount a response. VAFs contribute by presenting pancreas-derived fragments to inform the immune system while emitting anti-inflammatory cues that keep the immune response in check. When the pancreas experiences persistent inflammation—from infections, toxins, or environmental triggers—VAFs can become overwhelmed. In this overwhelmed state, the immune system may lose tolerance, triggering the autoimmune cascade that characterizes Type 1 diabetes.
Technology Driving the Insight
The researchers used a combination of advanced imaging, cell labeling, and single-cell analysis to study the pancreatic microenvironment. A notable tool, FucoID, developed at Scripps Research, enabled rapid identification and isolation of cells of interest. This approach helped map how VAFs recruit and retain subtypes of immune cells, and how their signaling may sustain islet cell protection even before overt disease.
Implications for Prevention and Treatment
Understanding VAFs reframes questions about Type 1 diabetes. Instead of asking only why the immune system attacks, scientists can investigate why the pancreas’ tolerance mechanisms fail and how to restore them. The implications extend beyond diabetes: similar tolerance pathways could influence autoimmune diseases and organ transplantation, where immune acceptance is critical.
From Discovery to Therapeutics
In the near term, researchers aim to develop therapies that bolster VAFs’ protective functions. Potential strategies include promoting states of anergy, reducing inflammatory triggers, and refining anti-inflammatory approaches that support these cellular peacekeepers. The goal is to shift treatment from broad immunosuppression to therapies that enhance the body’s own tolerance mechanisms.
With ongoing collaboration with Scripps Research Assistant Professor Joseph Jardine, the team is pursuing a deeper understanding of how VAFs regulate pancreatic immunity. They recently secured $3.2 million in funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to advance this work. If successful, such therapies could dramatically alter the standard of care for the 1.6 million Americans living with Type 1 diabetes and the countless others at risk around the world.
A Vision for Personalized, Tolerance-Driven Care
Ultimately, the researchers envision therapies that work with the body’s own protective systems. By enhancing VAF function or restoring tolerance after inflammatory bursts, clinicians could prevent disease onset or preserve insulin production in people with early-stage autoimmunity. This paradigm shift emphasizes precision medicine: tailoring interventions to bolster the pancreas’ natural peacekeeping mechanisms rather than suppressing immunity globally.
What’s Next?
The discovery marks an important milestone in diabetes research, but many questions remain. How exactly can VAFs be therapeutically boosted in patients? What are the long-term effects of targeted tolerance strategies? As studies progress from bench to bedside, the medical community remains cautiously optimistic about turning this new cellular insight into real-world benefits for people with Type 1 diabetes.
