Key Immune Cells in Gut Identified that May Halt IBD Progression

Leading institutions, including the Francis Crick Institute, King’s College London, and Guy’s and St Thomas’ NHS Foundation Trust, have illuminated a specific immune cell’s role crucial in maintaining a healthy human gut.

A concerning discovery indicates these essential immune cells decrease in number when inflammatory bowel disease (IBD) sets in, putting individuals at risk of rapid disease progression and severe health implications. This revelation paves the way for enhanced treatments and approaches for those battling IBD.

IBD, an umbrella term that covers Crohn’s disease and ulcerative colitis, pertains to severe inflammatory conditions in the gut. These conditions trigger intense gut inflammation, resulting in symptoms like intense pain and frequent diarrhoea. Alarmingly, about 1 in 125 UK residents suffer from IBD, with global figures on the rise. Notably, the onset often occurs during pivotal moments in a person’s life, such as early adulthood or childhood.

The recent study, featured in the journal Science, details an analysis of tissue samples from over 150 patients. The team focused on a predominant T cell population, gamma delta (γδ) T cells. Notably, a specialized version of these cells, V-gamma-4 (Vg4) cells, showed drastic changes and depletion in those with IBD.

Before this discovery, the Crick and King’s teams pinpointed molecules in the gut’s lining that communicate directly with Vg4 T cells. This new study probed whether any disruption in this relationship could be triggering IBD. Findings suggest that certain genetic factors, while not directly causing IBD, could increase the severity and progression of the disease.

Interestingly, for those who showed signs of inflammation subsiding, effective Vg4 T cell functions lowered the chances of an IBD relapse. Hence, monitoring Vg4 T cell activity could be pivotal in predicting IBD’s trajectory.

To explore this further, the researchers studied a select group of individuals possessing a gene that restricts this specific interaction. While having this gene didn’t necessarily make one more susceptible to IBD, it did amplify the risks of advancing the disease and intensifying complications for those already diagnosed with Crohn’s Disease.

Additionally, the team noticed that among individuals showing signs of reduced inflammation, those with rejuvenated Vg4 T cell activity had a diminished likelihood of a recurrence compared to their counterparts without such restoration. This implies that monitoring Vg4 T cell levels might serve as a valuable indicator of the disease’s trajectory.

Robin Dart, a distinguished researcher and clinician, commented, “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.”

Moreover, uncontrolled IBD has been linked with a heightened risk of colorectal cancer. Some even develop critical lesions, necessitating surgical procedures. Adrian Hayday, the research study’s lead, observed potential connections between these immune cells and aggressive forms of colon cancer.

Adrian Hayday, the lead author explained, “The links between uncontrolled IBD and particularly severe forms of colon cancer aren’t well understood. So, it’s fascinating that the key immune cell subset that we have identified as missing in IBD, may also be the same as the gut γδ T cells described by another group in Milan as having profound potential to attack colon cancer cells. We think that defects in these cells could conceivably link the two diseases.  

“I see gut γδ T cells as a vacuum cleaner clearing up damage done by infections and toxins coming in through a door which has to be kept open in order for food to pass through. If the γδ T cells aren’t working properly, damage accumulates, driving inflammation and potentially cancerous changes that can build to unchecked levels.”

The forthcoming phase of the study will delve into identifying prospective drug targets that can influence the interplay between γδ T cells and epithelial cells. Furthermore, refining methods to consistently track gut γδ T cells is pivotal, given their significance as indicators of IBD’s advancement or regression. Additionally, understanding the wider ramifications of this immune cell activity across various bodily regions will be crucial.

Image Credit: Shutterstock