Autoimmune diseases are a case of “mistaken identity”, i.e. the immune system that is supposed to protect us starts instead to attack our own tissues. Most autoimmune diseases have a strong genetic component, with candidate genes that increase risk or provide protection against the disease. Several autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, multiple sclerosis have as much as 30-50% of their candidate genes in common, raising the question on why in some individuals the immune system attacks, for instance, the insulin-producing beta cells, causing type 1 diabetes, while in others it targets joint tissues, leading to rheumatoid arthritis. Most of the research in the field has focused on the role for these candidate genes on the immune system, but work by Prof. Decio L. Eizirik, Welbio researcher at the ULB Center for Diabetes Research, Universite Libre de Bruxelles, and his co-workers indicated that many of these candidate genes affect the function and survival of pancreatic beta cells, leading to a misguided dialog between them and the immune system that culminates in diabetes. He has now, in collaboration with colleagues from Barcelona, Oxford, Pisa and the National Institute of Health, USA, clarified the role for pancreatic beta cells in type 1 diabetes, and provided an explanation for the reasons behind the immune system targeting beta cells under special conditions, for instance secondary to local inflammation caused by a viral infection or other “danger signals”. Thus, their observations indicate that binding of tissue-specific transcription factors (factors that regulate expression of specific genes, such as insulin, in beta cells) “opens” the chromatin (a complex of DNA and protein present in the cell nucleus) and allows binding of pro-inflammatory transcription factors induced in the beta cells by local inflammation. This is amplified in individuals genetically predisposed to type 1 diabetes, leading to generation of signals by the beta cells that contribute to attract and activate immune cells, rendering beta cells a potential target to the immune system.
Ramos-Rodríguez, M., Raurell-Vila, H., Colli, M. L., Alvelos, M. I., Subirana-Granés, M., Juan-Mateu, J., … Pasquali, L. (2019). The impact of proinflammatory cytokines on the β-cell regulatory landscape provides insights into the genetics of type 1 diabetes. Nature Genetics. https://doi.org/10.1038/s41588-019-0524-6