Inflammatory bowel disease linked to faulty immune cell

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The lasting nature of inflammatory bowel disease (IBD) may be due to a type of long-lived immune cell that can provoke persistent, damaging inflammation in the intestinal tract, according to a new study published in the journal Science Immunology.

For the study, the research team at the University of California San Diego School of Medicine, led by co-senior authors John Chang, MD, professor of medicine, and Gene Yeo, PhD, professor of cellular and molecular medicine, performed mRNA and antigen receptor sequencing from immune cells isolated from samples taken from rectal biopsies or blood of IBD patients and healthy controls.

IBD is a group of intestinal disorders affecting an estimated six to eight million people worldwide. Although there are many treatments for IBD, several patients fail to respond long-term, leaving those afflicted with a host of chronic issues, from abdominal pain and cramping to frequent, bloody stools.

It has long been believed that immune system dysfunction, in concert with genetic susceptibility and changes in the gut microbiome, plays a significant role in IBD. However, the types of immune cells involved and their specific contributions to IBD have remained unclear. CD8+ T cells are one component of the immune system that identify and kill cells infected by microbial pathogens.

When an infection has been conquered, the immune system leaves behind long-lasting cells called memory T cells, which reside in tissues or circulate through the body remembering past pathogens, ever ready to sound the alarm should specific invaders reappear.

The researchers discovered that there appear to be several subtypes of CD8+ tissue-resident memory T (TRM) cells, a specific class of memory cell that resides in organs once formed. One of these TRM cell subtypes was distinguished by high levels of the transcription factor eomesodermin and programmed to produce large amounts of cytokines and other molecules to kill newly detected infected cells. The downside is that excessive, persistently high levels of some cytokines can cause inflammation and tissue damage.

The researchers also found evidence that this inflammatory TRM cell subtype might not remain confined to intestinal tissue but may also escape into the bloodstream. Chang said the findings may help to explain why IBD is chronic and life-long, and point to the possibility of a remedy in the future, targeting this inflammatory TRM cell subtype for elimination, thus ending the cycle of inflammation and tissue damage.

"We found that this inflammatory TRMcell subtype seemed to be enriched in the intestinal tissues of patients with ulcerative colitis, a form of IBD that affects the colon," said Chang. "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."

The researchers said further research is needed to gain a deeper understanding of the role of tissue-resident memory T cells in IBD and to determine whether they can be targeted therapeutically.