image: The cells of the pancreas each play an important role in regulating the body’s blood sugar. Insulin producing cells (green) interact with the blood vessels and membranes (yellow) to disperse the hormone throughout the body. Scripps Research scientists recently identified a new cell called vascular-associated fibroblastic cells (red), which regulate the immune system and prevent autoimmunity.
Credit: Scripps Research
LA JOLLA, CA—Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks the cells that produce insulin—a critical hormone that regulates blood sugar in the body. Scientists at Scripps Research recently discovered a new kind of cell that helps protect insulin production, paving the way to understanding how researchers could prevent or reverse type 1 diabetes.
The new findings, published in Cell Reports on September 23, 2025, reveal how vascular-associated fibroblastic cells (VAFs) act as molecular peacekeepers in the pancreas—actively protecting insulin-producing cells from the immune system. This discovery helps explain several puzzling features of type 1 diabetes, including why the disease often has such a long preclinical phase—the symptom-free, early stage of the disease where the immune system is beginning to destroy insulin-producing cells, but blood sugar levels are still normal—and suggests that early intervention could be feasible in the future.
“Identifying these VAFs is an exciting step toward a better understanding of how the pancreas interacts with the immune system,” says Luc Teyton, professor in the Department of Immunology and Microbiology at Scripps Research and senior author of the study. “This finding unlocks a new understanding of autoimmunity and could help us design better therapeutics for type 1 diabetes and inform how we prevent or reverse the disease.”
For the 1.6 million Americans living with type 1 diabetes, managing the disease often requires time-consuming daily management. In addition to multiple daily insulin injections, blood sugar monitoring and a carefully regulated diet, type 1 diabetics face serious, life-threatening risks if their blood sugar levels aren’t within healthy ranges or well controlled.
To identify VAFs, Teyton and his lab took an unconventional approach that focused on the physiology and pathology of the pancreas. The team zeroed in on a site often responsible for inflammation—the post-capillary venules—and then used a combination of imaging, cell-labeling and single-cell analysis to examine how a healthy pancreas kept inflammation at bay. They used a cell-labeling technique, called FucoID, which was developed by Scripps Research professor Peng Wu and allowed the team to quickly identify and isolate cells of interest.
The researchers found that VAFs have a variety of specialized functions that prevent autoimmune attacks on insulin-producing cells. As immune cells travel around the body to detect danger or damage, they depend on antigen presentation—a process in which other cells display protein fragments to help determine whether an immune response is needed. VAFs participate in this process by presenting pieces of the pancreas, while also sending signals that placate the immune system and induce a tolerant state called anergy—thereby halting an autoimmune response.
The pancreas faces unique immunological challenges as part of the digestive system: it is constantly exposed to potential inflammatory triggers from food and the environment. Teyton and his lab identified that persistent inflammation of the pancreas—whether from infection, environmental toxins or other triggers—causes VAFs to become overwhelmed, forcing the immune system to activate and induce type 1 diabetes. Once in a state of overwhelm, autoimmunity proliferates in the pancreas—destroying the valuable insulin-producing cells that balance the body’s blood sugar levels.
“This discovery reframes how we think about type 1 diabetes,” says former Scripps Research postdoctoral researcher and first author, Don Clarke. “Rather than just asking why the immune system attacks, we can now ask: what disrupts the pancreas’ natural ability to maintain tolerance? And more importantly, how can we restore it?”
The protective nature of VAFs offers a new path for researchers to explore, shifting their focus to understanding how they can enhance the body’s natural tolerance mechanisms. Looking ahead, the team envisions developing therapies that strengthen VAFs’ specialized functions, such as increasing states of anergy and exploring anti-inflammatory treatments that could protect these cellular peacekeepers from being overwhelmed by inflammation. The work also has broader implications for understanding other autoimmune diseases and organ transplantation, where similar tolerance mechanisms may be at play.
As researchers advance these findings from laboratory discoveries to clinical applications, they aspire to develop personalized treatments that work with the body’s own protective systems rather than against them and potentially improve the outlook for millions at risk for type 1 diabetes. Teyton and his lab were recently awarded $3.2 million dollars by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to support this novel approach. In collaboration with Scripps Research Assistant Professor Joseph Jardine, the team aims to more deeply study and understand the role of VAFs as pancreatic cell peacekeepers. They also hope to develop therapeutic strategies that enhance or restore VAFs’ protective functions when overwhelmed by inflammation. This way, treatment options could prevent type 1 diabetes by strengthening the body’s own tolerance mechanisms, rather than broadly suppressing immunity.
In addition to Clarke and Teyton, authors of the study, “A vascular-associated fibroblastic cell controls pancreatic islet immunity,” include Anne Costanzo, Siddhartha Sharma, Lisa Kain, Peng Wu of Scripps Research; Kelley W. Moremen of the University of Georgia; Alain Domissy of University of California San Diego Medical School; Jeremy Pettus, Kim-Vy Nguyen-Ngoc, Denise Berti and Maike Sander of University of California San Diego; Steven C. George of the University of California Davis; and Christopher C.W. Hughes of the University of California Irvine.
This work was supported by grants from the NIH: the Clinical and Translational Science Award issued to the Scripps Translational Science Institute; UL1TR002550 and TL1TR002551 to D.C. and S.S.; 1R01 GM130915 to K.W.M.; 1R01AI143884 to P.W.; 1R01DK117138 to L.T.; UH3 DK122639 to M.S., C.C.W.H., and S.C.G.; BioF:GREAT, NSF 2400220 to K.W.M.; and UG3DK1421188 to C.C.W.H. and L.T.
About Scripps Research
Scripps Research is an independent, nonprofit biomedical research institute ranked one of the most influential in the world for its impact on innovation by Nature Index. We are advancing human health through profound discoveries that address pressing medical concerns around the globe. Our drug discovery and development division, Calibr-Skaggs, works hand-in-hand with scientists across disciplines to bring new medicines to patients as quickly and efficiently as possible, while teams at Scripps Research Translational Institute harness genomics, digital medicine and cutting-edge informatics to understand individual health and render more effective healthcare. Scripps Research also trains the next generation of leading scientists at our Skaggs Graduate School, consistently named among the top 10 US programs for chemistry and biological sciences. Learn more at www.scripps.edu.
Journal
Cell Reports
Article Title
A vascular-associated fibroblastic cell controls pancreatic islet immunity
Article Publication Date
23-Sep-2025