IBRI RESEARCH PUBLISHED: Revisiting the Role of Inflammation in the Loss of Pancreatic ß-cells in T1DM

August 28, 2020

Islet inflammation (insulitis) in type 1 diabetes mellitus is triggered by a deleterious dialogue between β-cells and the immune system, inducing β-cell dysfunction and death. This concept, outlined in our 2009 Review, has been confirmed and extended. Here, we provide a brief update of the field and outline key pending questions.

The background for our Review was the combination of a lecture and an undergraduate course. I (D.L.E.) was invited to present a lecture entitled “The helicopter view — the potential role of inflammation in type 1 diabetes (T1DM)” at a EASD–JDRF workshop in August 2008. At the time, I was teaching an undergraduate course focusing on innate immunity and its effect on four autoimmune diseases, including T1DM, and used the knowledge from the course to organize the ‘helicopter view’. The lecture was well received, and colleagues suggested that we should write a review based on it. After peer review, submission of a revised version of the text and preliminary acceptance, we were then surprised by the large number of changes introduced by the Associate Editor and the Art Department in the text and figures. After the initial shock, we realized that these changes were actually improving the manuscript, and from then on worked together with the Associate Editor to prepare the final version.

The two key messages of the article were that, first, innate immunity and inflammatory mediators contribute to the early induction and amplification of the immune response against β-?cells and then to the long-?term immune-?induced suppression and death of β-?cells in T1DM. Second, these effects of inflammation should be viewed in the context of a ‘dialogue’ between immune cells and the target β-?cells, a dialogue mediated by cytokines and chemokines and by immunogenic signals delivered by stressed or dying β-?cells. The article was well received and contributed to changing the prevailing ‘immune-?centred’ view of T1DM by suggesting that β-?cells are not inert victims of the immune system but participate in a deleterious dialogue that will lead to their eventual loss.

To read the complete review, go to Nature Reviews Endocrinology.