New research has linked inflammatory bowel disease (IBD) with a long lasting, overactive immune cell.
A new study has identified a link between IBD and the presence of a dysfunctional immune cell that continues to overreact for a long time.
The research, published in the journal Science Immunology, lays the groundwork for a better understanding of how and why IBD occurs and possible future therapies to treat the disease.
According to the Centers for Disease Control and Prevention (CDC), IBD is a general name for two diseases that involve the ongoing inflammation of a person’s gastrointestinal tract.
The gastrointestinal tract runs from the mouth to the anus and includes the esophagus, stomach, small intestine, and the large intestine. The final part of the gastrointestinal tract is the rectum, which leads out to the anus.
The two diseases associated with IBD are Crohn’s disease and ulcerative colitis. Crohn’s can affect any part of the gastrointestinal tract, from the mouth to the anus, though it most often affects the small intestine.
Crohn’s disease results in patchy, deep tissue damage, whereas ulcerative colitis damage is continuous, usually starting in the rectum and extending into the large intestine (the colon). The inflammation results in surface-level tissue damage.
The CDC highlight that both forms of IBD can result in diarrhea, pain in the abdomen, bloody stools, tiredness, and weight loss. While treatments for IBD have improved, some people still do not respond well over the long term.
In 2015, around 1.3% of adults in the United States received a diagnosis of IBD — a significant increase from 1999, where about 0.9% had the disease.
Scientists believe that a person develops IDB when their immune system overreacts, causing inflammation. However, they are less clear about what parts of the immune system does this, and why.
Two forms of analysis
To understand what role the immune system plays in IBD, a team of scientists from across the world conducted an experiment to analyze in detail the immune cells present in rectal biopsies or blood of people with IBD.
Since ulcerative colitis affects the same part of the gut in everyone who has it, scientists find it easier to study than Crohn’s disease. The scientists obtained samples from the rectum of seven people with ulcerative colitis and compared these with nine people who did not have the disease.
They used mRNA and antigen receptor sequencing. As Prof. Gene Yeo of the University of California San Diego School of Medicine and a co-author of the paper notes, “[w]e took advantage of a state-of-the-art approach allowing us to generate mRNA and antigen receptor sequencing data from the same single-cells and analyzed thousands of individual cells, which is quite exciting.”
Immune cells identify cells in a person’s body that a pathogen has infected and either neutralize the pathogen or kill the cell to get rid of it.
The T cells produce a specific response to each pathogen. Once the infection is over, they turn into memory T cells that circulate through a person’s body or lurk inside tissues — ready to respond immediately to the pathogen if it returns.
One type of these T cells is known as CD8+, which itself has various subtypes. One of the subtypes of memory CD8+T cells is resident in tissues. It is known as TRM.
T cell subtype
After analyzing the samples they had taken, the researchers found high levels of TRM in people with ulcerative colitis. Furthermore, it was in a hyper-excitable state.
Under the influence of an immune regulator known as Eomes, the TRM reproduced readily and produced a significant number of cytokines that damaged the person’s gastrointestinal tissue.
As Prof. John T. Chang, also of UC San Diego School of Medicine and a co-author of the paper highlights, “[w]e found that this inflammatory TRM cell subtype seemed to be enriched in the intestinal tissues of patients with ulcerative colitis, a form of IBD that affects the colon.”
“Long-lived memory cells are a goal of vaccines, but this finding suggests that these same cells, coveted in the fight against infectious diseases, may actually be harmful in the context of IBD.”
Further, the researchers found that this T cell subtype could also escape into a person’s bloodstream.
For Dr. Brigid S. Boland, a gastroenterologist at UC San Diego Health and co-author of the paper, “[t]his may explain why IBD can affect not just the intestines, but many other parts of the body as well.”
The researchers’ work opens the door to possible future treatments. However, the next step is to see if it is possible to target and eliminate this T cell subtype directly.