scRNA-Seq Study Links T Cell Subtypes to Chronic IBD

A new collaborative study—published in Science Immunology—led by scientists at the University of California San Diego School of Medicine, found that the lasting nature of IBD may be caused by a long-lived immune cell that provokes persistent, damaging inflammation to the intestinal tract. 

The team performed mRNA and antigen receptor sequencing from immune cells isolated from samples taken from rectal biopsies or blood of IBD patients and healthy controls. "We took advantage of a state-of-the-art approach allowing us to generate mRNA and antigen receptor sequencing data from the same single-cells," said co-senior author Gene W. Yeo, "and analyzed thousands of individual cells, which is quite exciting."

One of these T_^RM 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. However, the downside is that excessive, persistently high levels of some cytokines can cause inflammation and tissue damage.

"We found that this inflammatory T_^RM cell subtype seemed to be enriched in the intestinal tissues of patients with ulcerative colitis, a form of IBD that affects the colon," said senior co-author John T. 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 team also found evidence that this inflammatory T_^RM cell subtype might not remain confined to intestinal tissue, but may also escape into the bloodstream. "This may explain why IBD can affect not just the intestines, but many other parts of the body as well," said first author Brigid S. Boland.