New insights into how genetic factors affect the body’s immune response in type 1 diabetes have been published in eLife.
The findings provide evidence of a direct link between genetic factors associated with susceptibility to type 1 diabetes and immune functionality, especially involving immune T cells. They also highlight 11 genes that could be studied as potential candidates for new treatments.
Type 1 diabetes develops when the body’s immune system mistakenly attacks groups (or islets) of insulin-producing beta cells in the pancreas. There are currently over nine million people diagnosed with type 1 diabetes, but there is no cure and patients must receive regular insulin injections to manage the condition. People with certain genetic variations are more susceptible to type 1 diabetes. But while previous studies have identified about 60 related variations, it is not yet known how they affect the condition.
“To characterize the body’s immune response to type 1 diabetes, we need to look at both the proportion of immune cells and their production of proteins – cytokines – that stimulate the immune system,” said Xiaojing Chu, a doctoral student at the university. Groningen Medical Center, The Netherlands. Chu co-authored the study with Anna Jansen, MD, and Hans Coenen, an assistant professor at Radbud University Medical Center in the Netherlands. “In our study, we looked at how genetic factors affect immune cells and their production of cytokines in people with type 1 diabetes, as well as the differences between patients’ immune responses and health responses.”
To do this, the researchers collected blood samples from 243 volunteers of Dutch descent with type 1 diabetes, aged 20-84 years. They then applied a technique called genetic association analysis to more than 200 immune cell characteristics and more than 100 cytokine production profiles to identify the genetic determinants of immune functionality. They compare the results with those obtained in a group of 500 healthy individuals from previous studies, which characterize the impact of genetic factors on the immune responses in these individuals. *
Their analyzes show that the genetic variants that determine susceptibility to type 1 diabetes significantly affect T-cell composition. In particular, a group of these cells, called CCR5 + regulatory T cells, were actively involved in type 1 diabetes through a region of the genome called a restricted coding region.
The team then used a technique called genome-wide quantitative trait locus mapping (QTL) to analyze immune traits. This reveals 15 genetic “commands” that affect the behavior of immune cells in type 1 diabetes. Of these, 12 have not been previously reported in healthy people, suggesting disease-specific genetic regulation. In addition, the team identified 11 genes as potential candidates for drug development.
“Our findings provide a deeper understanding of the immune mechanisms involved in the development of type 1 diabetes and that influence the overall inflammatory response in patients. We hope that this work will open new avenues for the development of much-needed treatments,” concludes Yang Li. , Professor of Computational Biology and Director of the Center for Individualized Infectious Medicine (CiiM), Helmholtz Infection Research Center, Hanover, Germany. Lee is the co-senior author of the study with Seas Tack, a professor of internal medicine at Radbud University Medical Center in Nijmegen, the Netherlands.
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