Scientists hone in on DNA differences behind immune diseases
The search could help find drug targets for developing new treatments.
Scientists are one step closer to discovering the causes of immune diseases such as asthma, multiple sclerosis and arthritis. Research from the Wellcome Sanger Institute, GSK and Biogen, under the Open Targets initiative, has shown that thousands of differences in DNA between individuals, associated with immune diseases, are linked with the switching-on of a specific subtype of immune cells.
Published today (23rd September) in Nature Genetics, this study will help narrow down the search for the molecular pathways involved in immune diseases and could lead to finding drug targets for developing new treatments.
The immune system keeps us healthy by fighting infections. However, if something goes wrong, the cells in our immune system can mistakenly cause inflammation, leading to immune diseases like asthma, multiple sclerosis and inflammatory bowel disease (IBD). These diseases affect millions of people worldwide yet it is not known what triggers the immune system to respond in this way, or even the exact cell types involved.
Previous research found that there are thousands of genetic changes – known as genetic variants – that are more common in patients with immune diseases than in healthy people. Understanding these genetic changes could provide clues to the causes and biological pathways involved in immune disease, and in time, lead to identifying new drug targets.
Many of these genetic variants are in poorly understood areas of the genome and are thought to be involved in regulating functions of immune cells. Add to this, cytokines – the signalling proteins released to allow communication between the immune cells during inflammation – and the picture becomes even more complex, making it extremely difficult to pinpoint what is causing the disease.
Researchers at the Sanger Institute and their collaborators aim to understand which immune cell states are most important for immune diseases, in an effort to hone in on potential new drug targets for diseases like asthma and IBD.
In this new study, the team looked at which parts of the genome were active in three types of immune cells from healthy volunteers, and cross-checked these positions against all the genetic variants implicated in different immune diseases. They also added different cytokines, creating a total of 55 different cell states, to mimic immune disease inflammation and understand the effects of the signalling chemicals in these cells.
The study revealed that one particular cell type and cell state – early activation of memory T cells – had the most active DNA across the same regions as the genetic variants implicated in immune diseases. This pointed towards the initial activation of these T cells being important in disease development. Surprisingly, the research showed that the cytokines generally only had subtle effects on the DNA activity, and played a lesser role in most of the diseases studied.
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