In a first-of-its-kind experiment, researchers have identified links between 127 genes and immune diseases. The study provides new insights into the sequence and timing of gene activity during the activation of T cells, a key process in regulating the body’s immune response.
The study, published in Nature Genetics, is the result of a 3 year research effort. It is the first to show that many disease-linked variants are active during different stages of T cell activation. This could help to guide the development of new therapies for immune diseases such as rheumatoid arthritis, type-1 diabetes and Crohn’s disease.
T cell cycles
T cells are a group of white blood cells that help to manage the human immune system. When T cells malfunction, they can cause serious immune deficiencies. This can leave patients at high risk of infection, as well as more common autoimmune diseases such as type 1 diabetes and rheumatoid arthritis, where the body mounts an attack against its own cells.
Mapping the T cell activation cycle at a molecular level is crucial to understanding where it can go wrong, and at which points therapeutic interventions can influence the process. But previous techniques have been unable to describe the diversity of cell subtypes present at each step.
Identifying time specific genes
In this new study, researchers profiled over 650,000 individual cells using single-cell RNA sequencing. They mapped the timing of gene activity for each cell subtype in the T cell activation process.
The team identified over 6,400 genes involved in the activation process. By comparing their data with known genetic variants for 13 immune diseases, they were able to find 127 genes associated with those diseases. Some of these only manifested at certain time points which had not been previously studied.
“This unprecedented granularity is key to better understanding T cell activation, providing more in-depth data with which to pursue new treatments for immune disorders,” said one of the authors, Dr Blagoje Soskic from the Wellcome Sanger Institute.
Looking to the future
Follow up studies will need to alter each gene individually and examine how this affects the T cell activation process to recognise its exact function. This will provide vital insights into how immune processes can be affected by variations in DNA, and how immune-mediated diseases progress.
While this study centred on genes involved in 13 immune diseases, the approach and data generated can be applied to identifying genes involved in other disorders. The authors hope that this will highlight how diseases are related or underpinned by comparable biological processes. This work could also spotlight genetic risk factors. Overall, this study can guide drug discovery to create new and better therapies for immune-mediated conditions.
The authors noted, “Our data will provide crucial insight into key immune system mechanisms, helping us to understand which genes are affected, what might be causing disease, and what factors might be putting patients at risk.”
Written by Poppy Jayne Morgan, Front Line Genomics
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