Researchers have mapped out changes in T-cell activation—a key immune regulation process—moving the dial closer to discovering root causes of immune diseases, with Big Pharma GSK already using the science to inform early drug discovery.
Closing in on the intersection of gene activity and the immune system, the findings are the culmination of a three-year research effort from scientists at GSK and Open Targets’ Wellcome Sanger Institute in England. Published today in Nature Genetics, the research reveals multiple disease-linked variants working during different stages of T-cell activation—key information that could guide new treatment development for immune diseases such as rheumatoid arthritis, Type 1 diabetes and Crohn’s disease.
T cells are white blood cells crucial to combating infection, and abnormalities in functioning can lead to immune deficiencies and diseases. Researchers mapped T-cell activation at a molecular level, profiling over 650,000 individual cells using single-cell RNA sequencing technology. What they found was more than 6,400 genes tied to the activation process.
The researchers then compared their data with known genetic variants for 13 immune diseases. They identified links between 127 genes and immune diseases, some of which only manifest transiently at points never studied before.
Previously, only limited snapshots of T-cell activation had been mapped. Now, researchers were able to look across a range of time, while still zooming in at the single-cell level.
“Single-cell technology allows us to let the data lead and make much more precise hypotheses–rather than making assumptions,” David Tough, Ph.D., a senior scientific director in GSK’s Immunology Research Unit, said in a release.
The dynamic approach could shed light on how diseases are related and detect genetic risk factors.
“The learnings can be used in the future beyond the 13 diseases that were a part of this study to understand what’s underlying other diseases,” Tough explained. “For example, those in which T cells aren’t necessarily known to be involved but may play a role.”
The study is already informing the big pharma’s early discovery portfolio by “providing a novel, rich data set we are actively using to select genetically-informed drug targets for further validation experiments,” John Lepore, M.D., senior vice president and head of research at GSK, said in a news release.
Follow-up research in which scientists alter each gene individually to see how T-cell activation changes is still required.