A team led by Yasuhiro Murakawa at the RIKEN Center for Integrative Medical Sciences (IMS), Kyoto University in Japan, and IFOM ETS in Italy has discovered several rare types of helper T cells associated with immune disorders like multiple sclerosis, rheumatoid arthritis, and asthma. Published in *Science* on July 4, the findings were made using a new technology called ReapTEC, which identified genetic enhancers in these rare T cell subtypes linked to specific immune disorders. This new T cell atlas is publicly available and aims to aid in developing new drug therapies for immune-mediated diseases.
Helper T cells, a type of white blood cell, play a crucial role in the immune system by recognizing pathogens and regulating immune responses. Abnormal T cell function can lead to immune-mediated diseases, where T cells mistakenly attack the body (as in autoimmune diseases) or overreact to harmless substances (as in allergies). Recent studies have revealed the existence of rare and specialized T cells potentially related to these diseases.
Within T cells are DNA regions called “enhancers,” which, while not coding for proteins, enhance the expression of other genes through RNA. Variations in enhancer DNA can affect T cell function. The researchers developed ReapTEC to explore the connection between bidirectional T cell enhancers and immune diseases.
Analyzing about a million human T cells, the researchers identified several rare T cell types, accounting for less than 5% of the total. ReapTEC identified nearly 63,000 active bidirectional enhancers in these cells. Combining this data with genome-wide association studies (GWAS) revealed that genetic variants for immune-mediated diseases often resided within these enhancers. This pattern was specific to immune diseases, as neurological disease variants did not show similar associations.
The researchers pinpointed 606 bidirectional enhancers linked to 18 immune-mediated diseases and identified some of the genes targeted by these enhancers. For instance, activating an enhancer variant related to inflammatory bowel disease led to upregulation of the IL7R gene.
Murakawa stated, “In the short-term, we have developed a new genomics method that can be used by researchers worldwide. Using this method, we discovered new types of helper T cells and genes related to immune disorders. We hope this knowledge will lead to a better understanding of the genetic mechanisms underlying human immune-mediated diseases.”
The researchers believe that further experiments could identify new molecules for treating immune-mediated diseases.
