Researchers at the Francis Crick Institute, King’s College London, and Guy’s and St Thomas’ NHS Foundation Trust have characterized a specialized type of immune cell, which plays a key role in protecting and repairing the cells in the healthy human gut. These protective immune cells are depleted in inflammatory bowel disease (IBD), leaving patients vulnerable to disease progression and severe complications. The findings may lead to better treatment options.

Their study is published in Science in an article titled, “Conserved γδ T cell selection by BTNL proteins limits progression of human inflammatory bowel disease.”

The researchers investigated tissue from over 150 patients at Guy’s and St Thomas’ NHS Foundation Trust, dissecting a major population of T cells called gamma delta (γδ) T cells in the colons of people with healthy guts and people with IBD.

In healthy guts, there was a unique specialized subset of gamma delta cells, termed V-gamma-4 (Vg4) cells, that intriguingly were significantly altered and often conspicuously depleted in inflamed IBD samples.

Prior to this work, the team at the Crick and King’s had identified molecules in the healthy gut epithelium that directly interact with Vg4 T cells. So, in this new study, they tested whether losing this normal interaction between Vg4 T cells and the epithelium was underpinning disease.

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.

Robin Dart, PhD, 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.”

The next steps for the research are to investigate potential drug targets for the interactions between γδ T cells and the epithelial cells.