Jennifer Wang’s Lab Finds JAK Inhibitors Show Promise in Preventing Type 1 Diabetes
A newly published study from the laboratory of Jennifer Wang, MD, investigated the effects of type 1 interferon in type 1 diabetes using novel rat models.
Interferons are signaling proteins crucial in immune responses. Scientists have identified two main interferons involved in type 1 diabetes: type I (which includes interferon-alpha and beta) and type II (interferon-gamma). These proteins bind to specific cell receptors, triggering complex signaling pathways that affect gene expression and cellular behavior.
During research led by Wura Arowosegbe, PhD, the Wang lab used genetically modified rats lacking the type I interferon receptor (IFNAR) to investigate the mechanisms driving type 1 diabetes.
“We found that even without type I interferon signaling, some rats still developed diabetes, albeit at a lower rate and with delayed onset compared to normal rats,” said Dr. Wang, Professor in the Division of Infectious Diseases and Immunology and physician-scientist in the Diabetes Center of Excellence at UMass Chan Medical School. “This suggests that type II interferons or other factors also play a significant role.”
To further understand the disease process, they tested various inhibitors targeting different parts of the immune response. Blocking the Janus kinase (JAK) pathway, which is involved in both type I and type II interferon signaling, prevented diabetes in their rat model. They used a drug called ruxolitinib, which inhibits JAK1 and JAK2. It prevented diabetes when administered at disease induction, suggesting that JAK inhibitors might be a promising treatment to prevent type 1 diabetes in humans.
“This study highlights the complex interplay between different types of interferons and other immune factors in the pathogenesis of type 1 diabetes,” said Dr. Wang. “It shows that both types of interferons work together to cause the disease.”
The Wang lab’s rat model studies provide important clues about where to investigate next in their search for new ways to prevent and treat human type 1 diabetes.
Janus kinase inhibition prevents autoimmune diabetes in LEW.1WR1 rats
Adediwura Arowosegbe, Zhiru Guo, Emma Vanderleeden, Alan G Derr, Jennifer P Wang
PMID: 39823736 DOI: 10.1016/j.jaut.2025.103358
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