Diabetes: At the heart of the 'battle' leading to beta cell loss
Type 1 Diabetes (T1D) is caused by a misunderstanding from our immune system that attacks the insulin-producing pancreatic beta-cells. The very early steps of this process involve local release of pro-inflammatory mediators (cytokines) from immune cells that infiltrate the pancreatic islets where beta-cells are found. One of these mediators – a crucial one – is interferon-α (IFNα).
Pioneering research by Decio Eizirik (WELBIO – ULB) and his group at the ULB Center for Diabetes Research introduced a paradigm shift in the field. Their studies indicate that the “battle” between the beta cells and the immune system is fought, to a large extent, inside the beta-cells, and leads to a distorted “dialogue” with the invading immune cells that amplifies the immune assault, culminating in beta cell loss and ultimately T1D. Key components of this “dialogue” are the generation of potential beta-cells’ neoantigens by mechanisms such as alternative splicing and their presentation in the context of HLA class I to the immune system.
| The present study, published in Science Advances, clarifies a key step in the “misguided dialogue” between beta-cells and the immune system that eventually culminates in T1D. It was discovered that the expression of the transcriptional regulator NLRC5 is increased in beta-cells from pancreas donors with T1D and that the cytokine IFNα up-regulates NLRC5 expression in human beta-cells. Importantly, NLRC5 inhibition down-regulates IFNα -induced expression of HLA class I and other genes involved in antigen presentation, besides preventing the alternative splicing changes triggered by IFNα. This double role of NLRC5 on HLA class I expression and regulation of alternative splicing suggests that this transcription factor plays a pivotal role both in the generation of neoantigens and in their presentation to the immune system. |  |
Most research efforts to date to discover new treatments for T1D have focused on the immune system. Here, this study paves the way to search for therapeutic approaches to protect beta cells in the early stages of the disease.
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Source : ULB Press Release
