The researchers have identified a new target to treat patients with type 1 diabetes that blocks a protein called OCA-B. This protects the mice from type 1 diabetes by decreasing the activity of immune cells which in normal condition destroys the pancreas' insulin-producing β cells.
The research was conducted at the University of Utah School of Medicine and was published in the Journal of Experimental Medicine (JEM)
In type 1 diabetes, the body's immune system mistakenly attacks the pancreatic β cells, stopping the production of insulin. It is an autoimmune disease. These patients require life-long insulin therapy to control the blood-glucose levels. Currently, there are no treatment options that can stop the immune system from targeting β cells while still preserving its ability to fight infection.
In most of the autoimmune diseases, the T cells mistakenly recognize and respond to antigens which are produced by normal healthy cells.
Dean Tantin, professor at the Department of pathology University of Utah School of Medicine and also a member of the Huntsman Cancer Institute said, "Repeated antigen exposure is a common property of autoimmune responses. We therefore hypothesized that targeting OCA-B would inhibit autoreactive, diabetogenic T cell responses."
According to the study, the mice lacking OCA-B were protected from developing type 1 diabetes. Autoreactive cytotoxic T cells that can target and kill pancreatic β cells remained inactive and did not accumulate in the pancreas. Autoreactive helper T cells which recruit other immune cells to cause inflammation accumulate in the pancreas but remain non-responsive.
By chemically modifying the surrounding chromosomal DNA by recruiting an enzyme called Jmjd1a, OCA-B regulates the activity of T cell genes. The researchers developed a small peptide in the lab that was capable of stopping the association of OCA-B with Jmjd1a which prevented the reactivation of isolated T cells.
The activity of the autoreactive T cells can be reduced in pre-diabetic mice by injecting them with the small peptide. The glucose levels were restored to normal and the pancreatic inflammation was reduced.
Tanin said, "While the peptide is unlikely to be used in a clinical setting, it offers a proof-of-principle for OCA-B as a therapeutic target for type 1 diabetes, and can be used as a tool for the further development of therapeutics"