The gradual reduction in their regulating capacity seems to play a critical role in the onset of type 1 diabetes, as demonstrated in the latest study by Dr. Ciriaco Piccirillo, a researcher in the Department of Microbiology and Immunology at the Research Institute of the McGill University Health Centre and the principal investigator for this project. This study was published this month in the journal Diabetes.

The immune system needs to be regulated so that it attacks only the site of an inflammation and focuses its attack on pathogens rather than on the body tissues, causing an autoimmune disease.

In a healthy patient, CD4+Treg cells deactivate any T lymphocytes, a type of immune cell, that are misprogrammed and could attack the body. Dr Piccirillo's research indicates that in type 1 diabetic patients this control mechanism may be deficient, thereby allowing the misprogrammed T lymphocytes to proliferate and gain the ability to destroy the insulin-producing cells of the pancreas. This leads to type 1 diabetes.

We have been able to demonstrate this in mice with type 1 diabetes, and other genetic studies have shown that this same mechanism is applicable to humans, explained Dr. Piccirillo. Dr Piccirillo is an assistant professor at the McGill University, and the Canada Research Chair in Regulatory Lymphocytes of the Immune System. Furthermore, the predominant role of nTreg cells leads us to believe that they are also involved in other autoimmune pathologies. Finding this common denominator among diseases that were previously thought to be unrelated is a very promising avenue for future study, he adds.

Although the mechanism of action of CD4+Treg cells has not yet been completely unravelled, the scientific community generally accepts that this mechanism is of crucial importance to the entire immune system. Major fundamental and applied research efforts are currently being directed down this path and aim to clarify the role of CD4+Treg cells in order to develop innovative cellular therapies that could restore immune stability in patients.

The eventual hope is to treat the cause of type 1 diabetes and other autoimmune diseases and not just their symptoms, as we do today, says Dr Piccirillo.

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In the new study, Heimberg's team tied off a duct that drains digestive enzymes from the pancreas. That injury led to a doubling of beta cells in the pancreas within two weeks, they showed. The animals' pancreases also began producing more insulin, evidence that the new beta cells were fully functional, Heimberg said. He suspects the regenerative process is sparked by an inflammatory response in the enzyme-flooded pancreas.

They further found that the production of new beta cells depends on a gene called Neurogenin 3 (Ngn3), which is known to play a role in the pancreas during embryonic development.

The most important challenge now is to extrapolate our findings to patients with diabetes, Heimberg said. Although he cautioned that any potential diabetes treatment remains far into the future, our findings reveal the significance of investigating the feasibility of (1) isolating facultative beta cell progenitors and newly formed beta cells from human pancreas in order to expand and differentiate them in vitro and transplant them in diabetic patients and (2) composing a mix of factors able to activate beta cell progenitors to expand and differentiate in situ in patients with an absolute or relative deficiency in insulin, the researchers wrote.

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