Breakthrough Finds VAFs as Pancreatic Peacekeepers
In a landmark study published in Cell Reports on September 23, 2025, researchers from Scripps Research have identified a previously unrecognized group of cells that actively shield insulin-producing cells in the pancreas. These vascular-associated fibroblastic cells (VAFs) appear to act as molecular peacekeepers, helping to keep autoimmune attacks at bay and preserving the body’s ability to regulate blood sugar.
How VAFs Regulate Immune Tolerance in the Pancreas
The pancreas faces constant exposure to inflammatory triggers from food, infection, and environmental factors. The Scripps team led by Luc Teyton focused on post-capillary venules—sites frequently involved in inflammation—and used a combination of imaging, cell-labeling, and single-cell analysis to map how a healthy pancreas maintains immune tolerance. A key tool in their toolkit was FucoID, a cell-labeling technique developed by Scripps Research Professor Peng Wu, enabling rapid identification and isolation of relevant cells.
They found that VAFs engage in a sophisticated form of antigen presentation. While presenting pancreatic fragments to immune cells, VAFs simultaneously emit signals that temper immune responses and induce a state of anergy—a withdrawal from attacking the body’s own tissue. This dual role positions VAFs as crucial modulators in preventing autoimmune destruction of insulin-producing beta cells.
Implications for Type 1 Diabetes
Type 1 diabetes (T1D) arises when the immune system targets insulin-producing beta cells, disrupting blood sugar control. The discovery of VAFs provides a possible explanation for the disease’s long preclinical phase: inflammation can gradually overwhelm these peacekeepers, tipping the balance toward autoimmunity. If VAFs can be supported or reactivated, early intervention might maintain tolerance and stop progression before clinical symptoms emerge.
“This reframes how we think about type 1 diabetes,” says Don Clarke, a former Scripps Research postdoctoral researcher and the study’s first author. “Instead of asking only why the immune system attacks, we can examine what disrupts the pancreas’ natural tolerance—and how to restore it.”
Toward Therapies That Strengthen the Body’s Own Defenses
The immediate goal is to translate these insights into therapies that bolster VAF functions. Potential strategies include promoting states of immune tolerance (anergy) in the pancreas and developing anti-inflammatory approaches that prevent VAFs from becoming overwhelmed. Such therapies would align with precision medicine, aiming to reinforce the body’s inherent protective systems rather than broadly suppressing immunity.
The research team is already pursuing these directions with a new $3.2 million NIDDK grant to expand understanding of VAFs as pancreatic peacekeepers. Collaborating with Scripps Research Assistant Professor Joseph Jardine, the group intends to delineate how VAFs respond to inflammatory triggers and how their protective role can be restored or enhanced in people at risk for T1D.
A Bigger Picture for Autoimmune Disease and Transplantation
Beyond type 1 diabetes, the discovery of VAFs has broader implications for autoimmunity and organ transplantation. If similar tolerance mechanisms exist in other tissues, therapies designed to strengthen tissue-resident peacekeepers could reduce disease risk or improve graft survival by fostering local immune tolerance.
Looking Ahead
In the coming years, researchers hope to develop personalized interventions that work with the body’s own protective systems. The ultimate aim is to prevent type 1 diabetes or halt its progression by reinforcing VAFs’ ability to maintain a tolerant, inflammation-resilient pancreatic environment.
