Researchers from the University of Missouri School of Medicine are one step closer to understanding why some people develop type 1 diabetes.
Diabetes is a well-known condition where the body is unable to produce enough insulin, a hormone that helps regulate blood sugar levels. Genetics play a role in its development, but the two variants of the disease have different causes. Type 2 occurs due to a combination of factors, including being overweight and not being physically active. Type 1 is a hereditary autoimmune disorder where the body’s immune system attacks insulin production.
While it’s not fully understood why type 1 diabetes develops, a specific deficiency may be at play. Researchers discovered a specific protein that helps regulate immune system responses, IL-4, is low in nonobese diabetic mice.
“We found that the cells that produce IL-4, called iNKT cells, are also low in number in nonobese diabetic mice,” study author Habib Zaghouani said. “This suggests some sort of deficiency or malfunction in the thymus gland, which is also part of the immune system and where these cells are produced.”
Without enough IL-4 protein, too few dendritic cells are produced, which are immune cells that identify threats to the body. These immune cells can also detect T cells, also called lymphocytes or white blood cells, that attack body processes like insulin production and delete them, so they don’t cause further harm.
“In type 1 diabetes, the lack of IL-4 lets these self-reactive T cells do as they please, harming vital processes our body needs to function,” Zaghouani said.
Zaghouani plans to continue his research by determining why iNKT cells are low in number for individuals with type 1 diabetes. These answers could explain why type 1 diabetes develops, which would allow researchers to discover ways to prevent the disease.
Zaghouani says an injection containing supplemental IL-4 protein could strengthen the immune system against type 1 diabetes. He says such a treatment would need to undergo clinical trials to ensure safety and effectiveness.
Habib Zaghouani, PhD, is a professor of Molecular Microbiology and Immunology, Neurology and Pediatrics, and the director of the Immunity & Autoimmunity Research Lab. He is also the J. Lavenia Edwards Chair in Pediatrics.
“Reduced thymic IL-4 impairs negative T cell selection in nonobese diabetic mice” was recently published in the Journal of Clinical Investigation. In addition to Zaghouani, MU study authors include PhD graduate Alexis Cattin-Roy; Kimberly Laffey, assistant research professor of Molecular Microbiology and Immunology; Luan Le, senior undergraduate student; and Adam Schrum, associate professor of Bioengineering, Molecular Microbiology and Immunology and Surgery.
