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15 September 2023

Specialised gut immune cells pinpointed that can limit progression of inflammatory bowel disease

Researchers have shown how the presence of Vg4 T cells can reduce the risk of inflammatory bowel disease (IBD) relapse, which could not only be a new therapeutic avenue for IBD but also explain its link with colon cancer.

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Researchers at King’s, the Francis Crick Institute, and Guy’s & St Thomas NHS Foundation Trust have characterised a specialised type of immune cell, which plays a key role in protecting and repairing the cells in the healthy human gut.

Published in Science, the study looks at a group of immune cells called V-gamma-4 (Vg4) T cells. Prior research from a joint King’s-Crick team identified molecules that interact with these cells in the gut and this new study looked at whether losing this interaction influences inflammatory bowel disease (IBD).

The team found if individuals who have Crohn’s Disease and carry a rare gene that severely limits this interaction, they have a significantly increased risk of disease progression and developing severe complications. The researchers also observed that, in people whose IBD symptoms had improved, those with restored Vg4 T cell function were less likely to relapse than those who did not.

As well as being a potential new target for IBD therapy, this suggests that assessing the status of Vg4 T cells could be used to measure its progression. Investigating both angles will be the next step for this research.

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 V4 T cells may offer a way to do this.

Robin Dart, postdoctoral clinical research fellow in the School of Immunology & Microbial Sciences

IBD is the collective term for Crohn’s disease and ulcerative colitis, two currently incurable conditions which involve excessive inflammation in the gut, causing debilitating symptoms like pain and diarrhoea. IBD affects 1 in 125 people in the UK and is becoming more common.

People living with IBD are at an increased risk of developing colorectal cancer, especially when the disease is uncontrolled. This newly discovered connection between IBD and Vg4 T cells could also be one way that it’s linked to colon cancer.

The links between uncontrolled IBD and particularly severe forms of colon cancer aren’t well understood. It’s fascinating that V4 T cells that we have identified as missing in IBD, may also be the same as the gut γδ T cells also described as having profound potential to attack colon cancer cells. We think that defects in these cells could conceivably link the two diseases.

Adrian Hayday, Professor of Immunobiology in the School of Immunology & Microbial Sciences

In this story

Adrian  Hayday

Professor of Immunobiology

Robin Dart

Postdoctoral Clinical Research Fellow