Specialized gut immune cells identified that can limit progression of inflammatory bowel disease

Researchers from the Francis Crick Institute, King’s College London, and Guy’s and St Thomas’ NHS Foundation Trust have unveiled a specialized immune cell crucial for safeguarding and repairing the human gut’s healthy cells.

In conditions like inflammatory bowel disease (IBD), these protective immune cells are depleted, leaving patients susceptible to disease progression and severe complications. These findings may pave the way for enhanced clinical management and treatment options for those living with these ailments.

IBD encompasses Crohn’s disease and ulcerative colitis, both of which involve excessive gut inflammation, leading to debilitating symptoms such as pain and diarrhea. Affecting 1 in 125 people in the UK, IBD is on the rise globally and often begins in childhood or early adulthood, impacting critical life stages.

The study, featured in Science, involved analyzing tissue samples from over 150 patients at Guy’s and St Thomas’ NHS Foundation Trust, dissecting a significant group of T cells called gamma delta (γδ) T cells in the colons of individuals with healthy guts and those with IBD.

In healthy guts, a unique specialized subset of gamma delta cells, known as V-gamma-4 (Vg4) cells, was notably altered and frequently depleted in inflamed IBD samples.

Previously, the Crick and King’s teams identified molecules in the healthy gut epithelium (the gut wall lining cells) that interacted directly with Vg4 T cells. In this new study, they investigated whether the loss of this interaction contributed to the disease.

To explore this, the researchers examined individuals with a gene that severely restricts this interaction and found that while carrying this gene didn’t increase the risk of developing IBD, it significantly heightened the risk of disease progression and severe complications in those who already had Crohn’s Disease.

Furthermore, the study revealed that individuals with restored Vg4 T cell function were less likely to relapse if their inflammation had improved. This suggests that assessing Vg4 T cell status could serve as a valuable biomarker for disease progression.

Robin Dart, consultant gastroenterologist at Guy’s and St Thomas’ NHS Foundation Trust, emphasized the need to target areas beyond inflammation reduction, such as repairing the gut barrier, and highlighted the potential of γδ T cells, particularly Vg4 cells, in achieving this.

People with IBD face an increased risk of colorectal cancer, especially when the disease is uncontrolled, sometimes requiring surgical removal of cancerous or pre-cancerous gut lesions.

Adrian Hayday, principal group leader of the Immunosurveillance Laboratory at the Crick and Kay Glendinning Professor of Immunobiology at King’s College London, pointed out intriguing links between uncontrolled IBD and severe colon cancer. He suggested that defects in these immune cells might connect the two diseases.

Moving forward, the research will focus on identifying potential drug targets for γδ T cell interactions with epithelial cells and refining methods for routinely monitoring gut γδ T cells as a crucial marker for IBD progression and recovery. Additionally, the study aims to explore the broader implications of this immune cell biology in various body contexts.

This research was made possible through the consent of patients and support from the NIHR BioResource in providing additional samples.

Source: The Francis Crick Institute

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