Researchers have identified almost 100 unique genes that play an important role in immune diseases which could help lead to new treatments for conditions such as asthma, multiple sclerosis and type 1 diabetes.
Scientists at the Wellcome Sanger Institute conducted the first in-depth analysis of how genetic variants involved in immune diseases affect the function of regulatory T cells. The study, published in Cell Genomics1, could lay the groundwork for understanding the modulation of gene expression in these cells, providing valuable data for future studies and potential new treatments.
Regulatory T cells (Tregs) are a relatively rare immune cell type that play a key role in controlling human immune response. Previous studies have linked genetic variants that affect Treg function to immune diseases such as type-1 diabetes and rheumatoid arthritis. Studies have found that immune disease patients carrying Tregs do not function properly, or are present in abnormal numbers.
It’s thought that identifying how genetic variants modulate Treg function could have important clinical implications. However, the rarity of Tregs and the difficulty of culturing them in a lab means there are large gaps in scientists’ knowledge.
In the study, researchers Tregs from 124 healthy individuals to map how genetic variants regulated the expression of genes and function of the cells. Findings were then cross-referenced against variants associated with increased risk of developing immune diseases, in order to identify the genes that play pivotal roles in disease pathogenesis.
Patients that had genetic variants predisposing them to immune diseases were linked to a total of 91 genes, 31 of which were specifically impaired in Tregs but not in other immune cell types investigated by the researchers.
The researchers also identified seven drug targets that could be suitable for drug repurposing. A further 63 targets were found where there is drug tractability evidence – meaning a gene is suitable for drug development or there are already available drugs at some stage of clinical trials.
Dafni Glinos, a first author of the paper from the Wellcome Sanger Institute, said: “Regulatory T cells (Tregs) act as a break on the immune system to help it fight infection without escalating uncontrollably and harming the tissues of the body. If Tregs are not working as they should or are low in number, tissues can become too inflamed and result in immune disorders such as inflammatory bowel disease and arthritis. This study is an important step towards understanding how genetic variants influence the function of Tregs and what role this can play in disease.”
The next step for this research will be to investigate precisely how genes affect Treg function by simulating these interactions in the laboratory, which will provide more context for the development of new therapies.
1: Lara Bossini-Castillo and Dafni A. Glinos et al. (2022). Immune disease variants modulate gene expression in regulatory CD4+ T cells. Cell Genomics. DOI: https://doi.org/10.1016/j.xgen.2022.100117