- Scientists say they have identified a unique type of immune cell that has a pivotal role in protecting and revitalizing cells within the human intestinal tract.
- In individuals with inflammatory bowel disease (IBD), there is a reduction in these protective immune cells, increasing the risk of disease advancement and serious complications.
- This new research holds promise for better management and treatment of IBD, a condition that includes Crohn’s disease and ulcerative colitis.
Inflammatory bowel disease (IBD) includes Crohn’s disease and ulcerative colitis, both of which currently have no cure and are characterized by heightened gut inflammation that can result in symptoms such as pain and diarrhea.
In a new study, published in the journal Science, researchers examined a group of T cells known as gamma delta (γδ) T cells in the colons of individuals with healthy intestinal tracts and those with IBD.
The researchers said they identified a distinct specialized subset of gamma delta cells called V-gamma-4 (Vg4) cells, which were notably altered and often noticeably diminished in the inflamed samples of individuals with IBD.
Before conducting this research, the team from the Crick Institute and King’s College London had previously identified molecules in the healthy gut epithelium (the cells that line the gut walls) that directly engage with Vg4 T cells.
They examined whether the disruption of this normal interaction between Vg4 T cells and the epithelium was a fundamental factor in the development of the disease.
The study involved samples from more than 150 people treated at Guy’s and St Thomas’ NHS Foundation Trust.
Robin Dart, a first study author and former PhD student at the Crick as well as a postdoctoral clinical research fellow at King’s College London and a consultant gastroenterologist at Guy’s and St Thomas’ NHS Foundation Trust, explained the key findings to Medical News Today.
The Inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis, are chronic relapsing and remitting conditions of increasing global incidence. The intestine is covered by a single-cell lining which protects the body from the contents of the gut and is impaired in IBD. This lining contains specialized cells called gamma delta T cells.
Robin Dart
“In this study we identify a unique subset of these gamma delta T cells called V-gamma-4 cells which are present in the healthy intestine and we find that they are altered in IBD,” Dart said.
“We found a gene that leads to a loss of these V-gamma-4 cells. People with Crohn’s disease who carry this gene were more likely to have severe disease, indicating that these cells are important in protecting people from severe disease,” he added.
“Furthermore we investigated a small group of people who had had successful treatment [before the study] and healed their intestines. In the healed intestine, those patients who had V-gamma-4 cells like those we see in healthy people, had higher rates of long-term remission,” Dart explained.
During the study, the researchers noticed that among individuals whose inflammation had improved, those with restored Vg4 T cell function had a lower likelihood of experiencing a relapse compared to those without this restoration.
They said that this implies that evaluating the condition of Vg4 T cells could serve as a valuable indicator for tracking the advancement of the disease.
Current treatments mainly concentrate on reducing inflammation, but even with advancements in therapy, disease relapses continue.
Therefore, the researchers said, it is imperative to explore alternative avenues, such as the restoration of the gut barrier, and γδ T cells, specifically Vg4 cells.
The researchers said that individuals living with IBD face an elevated risk of developing colorectal cancer, particularly when the disease is uncontrolled.
In certain cases, individuals develop cancerous or precancerous lesions in the gut, necessitating surgical removal.
The connection between uncontrolled IBD and the development of severe forms of colon cancer is not well understood. Therefore, researchers said it is important that the crucial subset of immune cells identified as absent in IBD may align with the gut γδ T cells.
The researchers believe that defects in these cells could potentially serve as a link between the two diseases.
They view gut γδ T cells as akin to a vacuum cleaner that clears up damage caused by infections and toxins entering through a door that must remain open for food to pass through.
When γδ T cells do not function properly, damage accumulates, leading to inflammation and potentially cancerous alterations that can progress unchecked.
Future research will involve exploring possible pharmaceutical targets for the interactions between γδ T cells and epithelial cells and enhancing methods for regularly monitoring gut γδ T cells, which are essential as markers for distinguishing between the progression and recovery of IBD.
According to Dr. Blen Tesfu, a general practitioner who was not involved in this research, the study paper “presents intriguing research on the role of γδ T lymphocytes in the human gut and their potential implications for understanding and treating IBD.”
IBD is a challenging and chronic condition that affects a significant number of people globally. Any research that sheds light on its underlying mechanisms and offers potential new treatment avenues is of great public health importance. This work could ultimately improve the quality of life for IBD patients and reduce the burden of the disease.
Dr. Blen Tesfu
Tesfu pointed out that “the depletion and dysregulation of BTNL-selected γδ T cells in IBD patients raise the possibility of targeting these cells to promote tissue surveillance and repair.”
“This could potentially lead to new treatment modalities for IBD that go beyond anti-inflammatory agents,” Tesfu said.
Dart noted how they “have implicated an important pathway to be studied in not only inflammatory bowel disease but the human colon in general.”
“During this study we have been able to develop new tools with which to study gamma-delta T cells and it is now very important to use this as a springboard for more investigation in IBD and other conditions including cancer,” he said.
“We need to better understand the restorative functions of V-gamma-4 cells and how we stimulate and restore this compartment to prevent complications of disease,” Dart added.
Long term, understanding using knowledge generated in this paper to better care for patients is the ultimate aim, be that through biomarkers to help direct therapeutics with more precision or through novel therapies which aim to harness the power of human gamma-delta T cells to provide durable healing to the gut epithelium.
Robin Dart
