Newly Published Study Provides Clues About the Autoimmune Attack in Type 1 Diabetes
Date Posted: Thursday, July 24, 2025
The UMass Chan Medical School’s Diabetes Center of Excellence (DCOE) contributed to type 1 diabetes research that sheds light on how the immune system attacks insulin-producing beta cells in the pancreas. They examined human pancreatic islets, which contain all the body’s beta cells, induced with stress caused by inflammatory molecules called cytokines. They found that this stress changes how these cells present themselves to the immune system. Specifically, exposure to cytokines alters the way islet cells display tiny protein fragments, or 'antigens.'
Their findings, published in Cell Reports, show that cytokine stress causes islet cells to present new types of antigens. These new antigens may attract immune cells and fuel the attack that destroys insulin-producing cells in type 1 diabetes.
“For decades, we have been trying to understand why the immune system attacks the very cells meant to keep our blood sugar balanced,” said Sally Kent, PhD. “This research brings us closer to solving that mystery by showing how stress changes the ‘face’ these cells present to the immune system.”
The collaborative research involved the laboratories of Dr. Kent; Jennifer Wang, MD; and Sam Redick, PhD, a senior scientist in the laboratory of David Harlan, MD. The study was led by Lawrence Stern, PhD, professor of pathology at UMass Chan.
The Antigen Presentation Landscape of Cytokine-Stressed Human Pancreatic Islets
Nanaware PP, Calvo-Calle JM, Redick SD, Tarpley MW, Cruz J, Clement CC, Manganaro A, Velarde de la Cruz EE, Muneeruddin K, Faulkner M, Wang JP, Shaffer SA, Harlan DM, Santambrogio L, Kent SC, Stern LJ. Cell Rep. 2025 Jul 18;44(8):115927. doi: 10.1016/j.celrep.2025.115927. Online ahead of print. PMID: 40684438
“If we can learn how these new antigens are formed and displayed when beta cells are stressed, it could help us to develop ways to shield those cells from immune attack,” added Dr. Kent. “That could be a game-changer for people living with or at risk of type 1 diabetes.”
These are the types of studies that the DCOE regularly conducts to get a better understanding of the autoimmune process that leads to type 1 diabetes. At the same time, DCOE scientists are actively working toward a cure.
“We can now grow human islet cells in a test tube and investigate them,” said Dr. Harlan, co-director of the UMass DCOE. “With new genetic tools, we are getting closer to making those cells resistant to immune destruction.”
The goal is to develop therapies that restore insulin production without the need for lifelong immunosuppressive drugs, ultimately leading to a cure.
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