Healthcare (Commonwealth Union) – When it comes to Type 1 diabetes, it is an autoimmune condition where an individual’s immune system mistakenly targets the insulin-producing cells, which are vital for the maintenance of blood sugar levels. Scientists from Scripps Research have recently marked a previously unknown type of cell that gives its assistance to safeguard insulin production. This gives new insights into the way type 1 diabetes might one day be preventable or reversible.
Appearing in Cell Reports on September 23, this year, the research highlights the way vascular-associated fibroblastic cells (VAFs) play a role as molecular guardians in the pancreas, actively guarding insulin-producing cells from an attack by the immune system. This key finding gives insights to some of the longstanding mysteries of type 1 diabetes, which include the reason why the disease often forms slowly during a symptom-free period when the immune system is already damaging insulin-producing cells but blood sugar levels stay consistant.
It also points to the potential for early therapeutic intervention in the future.
Luc Teyton, professor in the Department of Immunology and Microbiology at Scripps Research and senior author of the paper indicated that discovering these VAFs is a major step forward in understanding how the pancreas communicates with the immune system.
He further pointed out that this finding opens up new avenues for studying autoimmunity and could lead to improved treatments for type 1 diabetes, as well as strategies to prevent or reverse the condition.
Even though the percentage of individuals living with type 1 diabetes is much lower than those with type 2 diabetes, managing the condition often demands is different. Type 1 diabetes requires constant, time-intensive attention. Beyond multiple daily insulin injections, regular blood sugar checks, and strict dietary control, individuals with type 1 diabetes face serious, potentially life-threatening consequences if their blood sugar is not properly regulated.
To uncover vascular-associated fibroblastic cells (VAFs), Teyton and his team adopted an unconventional strategy centered on the pancreas’s physiology and pathology. They focused on a region commonly linked to inflammation—the post-capillary venules—and employed a combination of imaging, cell-labeling, and single-cell analysis to investigate how a healthy pancreas prevents inflammatory responses. They utilized a cell-labeling method called FucoID, developed by Scripps Research professor Peng Wu, which enabled rapid identification and isolation of the cells of interest.
The scientists noted that VAFs perform many specialized roles that guard insulin-producing cells from autoimmune attacks. As immune cells put the body under surveillance seeking out threats or tissue damage, they are dependant on antigen presentation. This is where cells display protein fragments to direct the immune system to respond. VAFs contribute to this mechanism by presenting pancreatic fragments while simultaneously sending calming signals that induce immune tolerance, known as anergy, effectively halting autoimmune activity.
Teyton’s study shows that chronic inflammation—whether caused by infection, atmospheric toxins, or others, may have an overwhelming effect on VAFs. When this takes place, the immunity becomes activated, bringing about type 1 diabetes. When these guard cells are compromised, autoimmune processes get elevated in speed. This damages the insulin-producing cells crucial for keeping a balance of blood sugar levels.
“This discovery reframes how we think about type 1 diabetes,” explained the 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 role of VAFs opens a fresh avenue for researchers, encouraging a focus on how to boost the body’s natural tolerance systems. Moving forward, the team aims to develop therapies that enhance VAFs’ unique functions, such as promoting anergy and investigating anti-inflammatory approaches to shield these cellular guardians from excessive inflammation. Beyond type 1 diabetes, this research may also shed light on other autoimmune conditions and organ transplantation, where comparable tolerance mechanisms could be crucial.
The scientists hope to use this discovery to develop more personalized treatments.
