According to the Crohn's & Colitis Foundation, 1.6 million Americans have irritable bowel syndrome (IBD), and the number is increasing every year. There are approximately 70,000 new cases diagnosed every year.
Robin Dart, consultant gastroenterologist at Guy's and St Thomas' NHS Foundation Trust, said: "There is currently no cure for IBD, and for a significant proportion of the patients I treat, ongoing relapses are distressing and seriously impact on their daily lives. Treatment often focuses on reducing inflammation, but despite improvements in therapy, relapse rates remain high."
The good news is that recent advances in genetics, immunology and microbiology are giving scientists a deeper understanding of the disease and how to better focus research to develop innovative treatments.
Dart and a collaborative team of researchers from the Francis Crick Institute, King's College London and Guy's and St Thomas' NHS Foundation Trust have now characterized the V-γ-4 (Vg4) subpopulation of specialized T cells, which play a key role in intestinal lining protection and repair.
"We need to start targeting other areas, such as repairing the intestinal barrier, and gamma delta T cells, especially Vg4 cells, may provide a way to do that," Dart said.
Researchers looked at healthy and IBD colon tissue samples from 150 patients and found significant differences in gamma delta (γδ) T cells between the two groups. In the healthy gut, they found a robust population of Vg4 T cells, but in the tissue of IBD patients this subset of cells was different and, in many cases, severely depleted.
Lead author Adrian Hayday, professor of immunobiology at King's College London, said: "I think of intestinal gamma delta T cells as being like a vacuum cleaner, cleaning up the damage caused by infections and toxins. If gamma delta T cells are not working properly, the damage can accumulate, triggering inflammatory and potentially cancerous changes, and may progress to the point of being uncontrollable."
If these protective immune cells are depleted, the gut becomes vulnerable to disease progression. Patients with poorly managed IDB are at higher risk of developing colorectal cancer.
"The link between uncontrolled IBD and a particularly severe form of colon cancer is not well understood," Haidai said. "So it was fascinating that we discovered that a key subset of immune cells missing in IBD may be the same intestinal gamma delta T cells described by another research group in Milan as having great potential to attack colon cancer cells. We believe that defects in these cells have the potential to link the two diseases."
The researchers also found that IBD patients whose Vg4 T cell populations returned to normal function were less likely to relapse after an inflammatory episode than those who did not.
These findings have the potential to lead to better clinical treatments for IDB and provide more acute markers for monitoring disease progression and recovery.
The research was published in the journal Science.