Scientists have long 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, scientists have been trying to determine why insulitis sometimes leads to diabetes (so-called "destructive" insulitis) and sometimes does not ("innocuous" insulitis).
To study this question, Laurent Poirot, Ph.D., Christophe Benoist, M.D., Ph.D., and Diane Mathis, Ph.D., of the Section on Immunology and Immunogenetics at Joslin Diabetes Center in Boston looked at two related strains of genetically engineered mice -- one whose insulitis is known to be destructive and the other whose insulitis is innocuous. Using powerful genetic tools known as microarrays, which allow the researchers to test for thousands of genes at once, they looked for differences in gene expression between the cells causing innocuous insulitis and those causing destructive insulitis.
The researchers discovered that there was a greater expression of genes characteristic of natural killer cells, and more of these cells, in the destructive insulitis lesions compared with innocuous lesions. "That was a surprise because NK cells had previously not been thought to promote diabetes," explained Mathis. "In fact, if anything, they were thought to protect against it." Mathis and Benoist hold the William T. Young Chair in Diabetes at Joslin and co-head the Section of Immunology and Immunogenetics. Both are professors of medicine at Harvard Medical School.
Furthermore, when the researchers treated the diabetes-prone strain of mice with various reagents that depleted the NK cells, this lowered the incidence of overt diabetes. "We now believe that NK cells play an important role in the destruction of beta cells, especially in rapidly progressing type 1 diabetes," Benoist said. "If NK cells are important for the progression of diabetes in humans, and we can block them, we may some day be able to exploit such a strategy to halt or slow the progression of the disease."
An estimated 800,000 Americans have type 1 diabetes, in which the insulin-producing beta cells of the pancreas have been destroyed. They 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 of its forms, is the global leader in diabetes research, care, and education. Joslin is uniquely qualified to lead the battle against diabetes in the 21st century. 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 for 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.
Journal
Proceedings of the National Academy of Sciences