A research team led by Decio Eizirik, Director of the ULB Center for Diabetes Research and WELBIO investigator, is working to understand the mechanisms that lead the immune system to recognize the patient’s own beta cells as foreign and attack them. A new study, published in Cell Metabolism, will contribute for a better prediction of the disease and open novel perspectives for the development of approaches to induce tolerance to the beta cells.
Around 600.000 individuals are affected by diabetes in Belgium and around 10% of these patients suffer from type 1 diabetes, an autoimmune disease characterized by the progressive loss of pancreatic beta cells. These cells secrete insulin, a crucial hormone to maintain a normal glucose concentration in the blood and allow glucose to enter the liver, muscles, adipose tissue etc.
In type 1 diabetes the immune system makes a terrible mistake: while it is supposed to protect us against infections or cancers, in this case it starts recognizing some proteins expressed by the beta cells as foreign and attacks them. This leads to the progressive death of beta cells, culminating with their disappearance, which forces the patients to inject insulin several times a day, for the remaining of their lives.
Around 50% of the pancreatic beta cell antigens (protein fragments recognized by the immune system) recognized by the immune system in type 1 diabetes have already been identified. The nature of the remaining 50% antigens remains, however, unknown. This creates major obstacles to predict the disease and to induce tolerance to these antigens and thus protect beta cells.
In the context of a collaboration with the Institute Cochin, INSERM, Paris (led by Prof. Roberto Mallone), and several other European laboratories, Decio L. Eizirik and his team published a study in which the researchers utilized advanced molecular biology and bioinformatics techniques to identify the beta cell “image” perceived by the immune system, particularly by the CD8 positive cells, a key cellular type for the destruction of beta cells. They identified several new beta cell antigens recognized by the immune system and showed that at least three of them are targeted by immune cells in the pancreas of patients affected by type 1 diabetes, indicating their relevance for the induction of diabetes.
This study opens the way for a better understanding of the mechanisms leading to the recognition of beta cells by the immune system. Furthermore, they may lead to the generation of novel tools to predict the disease and to develop “tolerogenic vaccines” aiming to prevent or revert the recognition of beta cells by the immune system.
References : Sergio Gonzalez-Duque et al. (2018) Conventional and neo-antigenic peptides presented by β cells are targeted by circulating naïve CD8+ T cells in type 1 diabetic and healthy donors. Cell Metabolism. DOI : https://doi.org/10.1016/j.cmet.2018.07.007