Joslin researchers identify key molecule in Type 1 diabetes progression
For many years scientists have known that type 1 diabetes is an autoimmune disease in which the body's immune system mistakenly launches an attack on the insulin-producing beta cells of the pancreas. At an early stage in this process, white blood cells called T-cells invade the islets of Langerhans of the pancreas, where the beta cells reside (a condition known as "insulitis"). Yet, in both mice and humans, insulitis does not always progress to full-blown type 1 diabetes.
For years, researchers have been trying to determine why insulitis sometimes leads to diabetes (so-called "destructive" insulitis) and sometimes does not ("respectful" insulitis). They know that certain T-cells called T effector cells promote destructive insulitis, and other T-cells called regulatory T-cells favor respectful insulitis. Yet, no one knows exactly what causes the balance of power to shift between these two types of cells to cause diabetes.
To study this question, Anne E. Herman, Ph.D., Diane Mathis, Ph.D., and Christophe Benoist, M.D., Ph.D., of the Section on Immunology and Immunogenetics at Joslin Diabetes Center in Boston studied insulitis lesions in a certain strain of genetically engineered mice called BCD2.5 mice. These mice develop insulitis, but a very respectful form, such that diabetes does not follow until months later, or, in some, never. The researchers discovered that both effector and regulatory T-cells co-existed and thrived in these insulitis lesions, and they wondered what kept these lesions respectful.
They looked specifically at a molecule called inducible co-stimulator (or ICOS), which was expressed at an unusually high level on regulatory T cells. Using monoclonal antibodies (man-made versions of natural antibodies, which target individual proteins like guided missiles), the researchers blocked the action of ICOS to see what would happen. Blocking ICOS disrupted the balance between T effector and T regulatory cells, and provoked insulitis to immediately convert to diabetes. The researchers concluded that ICOS plays an important role in keeping insulitis lesions from becoming destructive.
"Understanding the molecular and cellular basis of the immune regulation in the lesion might some day lead to the development of therapies that favor regulatory T-cells and respectful insulitis, preventing the development of full-blown diabetes even after insulitis has developed," Herman explains.
Mathis and Benoist hold the William T. Young Chair in Diabetes at Joslin and co-head the Section on Immunology and Immunogenetics. Both are Professors of Medicine at Harvard Medical School. The research was funded by the National Institutes of Health and the Juvenile Diabetes Research Foundation. Gordon J. Freeman, Ph.D., of the Dana Farber Cancer Institute collaborated on the study.
In type 1 diabetes, which affects an estimated 800,000 Americans, the insulin-producing beta cells of the pancreas have been destroyed. People with type 1 diabetes must take insulin to survive, and are at greater risk for heart attack and stroke, as well as diabetes-related diseases of the eyes, kidneys, and nerves. Currently, type 1 diabetes cannot be cured, but by keeping their blood glucose levels as close to normal as possible, many people with diabetes can prevent or slow down the long-term complications of the disease.
Joslin Diabetes Center, dedicated to conquering diabetes in all its forms, is the global leader in diabetes research, care and education. Joslin Research is a team of over 300 people at the forefront of discovery aimed at preventing and curing diabetes. Joslin Clinic, affiliated with Beth Israel Deaconess Medical Center in Boston, the nationwide network of Joslin Affiliated Programs, and the hundreds of Joslin educational programs offered each year to clinicians, researchers and patients, enable Joslin to develop, implement and share innovations that immeasurably improve the lives of people with diabetes. As a nonprofit, Joslin benefits from the generosity of donors in advancing its mission. For more information on Joslin, call 1-800-JOSLIN-1 or visit www.joslin.org.
For more information or to schedule interviews, contact:
Marge Dwyer or Jenny Eriksen, Joslin Communications, 617-732-2415.
Contact: Marge Dwyer
marjorie.dwyer@joslin.harvard.edu
617-732-2415
Joslin Diabetes Center
Joslin cercetãtori identifica moleculã cheie în progresia diabet zaharat de tip 1 - Joslin researchers identify key molecule in Type 1 diabetes progression - articole medicale engleza - startsanatate