Researchers from the Francis Crick Institute, King’s College London and Guy’s and St Thomas’ NHS Foundation Trust in the UK have characterised a specialised type of immune cell, which plays a key role in protecting and repairing the cells in the healthy human gut.
The researchers found that in healthy guts there was a specialised subset of gamma delta T cells (V-gamma-4 (Vg4) cells) that were significantly altered and often depleted in inflammatory bowel disease (IBD) samples.
The team at the Crick and King’s had previously identified molecules in the healthy gut epithelium which directly interact with Vg4 T cells. They tested whether losing this normal interaction between Vg4 T cells and the epithelium was underpinning disease.
To do this, the team looked at relatively rare individuals carrying a gene that severely limits this interaction, and found that whereas carrying this gene didn’t increase the chance of developing IBD, for those who already developed Crohn’s Disease, it significantly increased the risk of disease progression and the development of severe complications.
The researchers also observed that, in people whose inflammation had improved, those with restored Vg4 T cell function were less likely to relapse than those who did not. This suggests that assessing the status of Vg4 T cells could be a useful biomarker for disease progression.
Potential drug targets to be investigated
Robin Dart, former Wellcome trust funded PhD student at the Crick, postdoctoral clinical research fellow at King’s College London, and Consultant Gastroenterologist at Guy’s and St Thomas’ NHS Foundation Trust, said: “There’s currently no cure for IBD, and for a significant proportion of the patients I treat, persistent relapses are distressing, severely impacting their day-to-day lives.
“Treatments tend to focus on reducing inflammation, but despite improvements in therapy, relapse rates remain high. So, we need to start targeting other areas, such as repairing the gut barrier, and γδ T cells, particularly Vg4 cells, may offer a way to do this.”
People living with IBD are at an increased risk of developing colorectal cancer, especially when the disease is uncontrolled.
The next steps for the research are to investigate potential drug targets for the interactions between γδ T cell and the epithelial cells and to refine approaches for routinely monitoring gut γδ T cells as a much-needed marker for IBD progression versus recovery.
