Researchers in Oxford using an ‘atlas’ of immune cells in the human colon have found evidence of the role of CD8 T cells in inflammatory bowel disease (IBD).
The findings could lead to a better understanding of how cells behave and interact in people with IBD, and could pave the way for more targeted treatments for this chronic disorder.
IBD, which includes Crohn’s disease and ulcerative colitis, affects more than 2 million people in Europe and 1.5 million in North America, and its incidence is increasing in countries undergoing urbanization.
The study, published in Nature Medicine, was carried out by a team from the University of Oxford’s MRC-Human Immunology Unit, Weatherall Institute of Molecular Medicine, supported by the NIHR Oxford Biomedical Research Centre (BRC).
IBD is a chronic inflammatory disorder thought to be caused by a breakdown in the way the immune system responds to gut bacteria.
Although there is no cure for IBD, biological therapies have revolutionised care for those living with the condition. However, a significant proportion of patients fail to respond to treatment, partly due to our limited understanding of molecular and functional heterogeneity of individual cell populations living in the intestinal mucosa.
The Oxford researchers used multi-modal single-cell technologies to compile an atlas of human colonic T cells in healthy individuals and in those with ulcerative colitis. They focused in particular on CD8 T cells, a population of T cells present in high quantity in the intestinal mucosa, that possess immune killing activity which may be unleashed inappropriately in inflammatory diseases.
One of the authors, Dr Daniele Corridoni, said: “Despite some evidence that CD8 T cell contribute to IBD pathology, little was known about the extent of variation, transcriptional regulation and relatedness of the cells that make up this population in the intestinal mucosa.
“Our study is the first of its kind to describe in an unbiased manner the different subpopulations of cells within intestinal CD8+ T cells and which of those contribute to inflammation.”
The group used multi-modal single cell profiling of CD8+ cells isolated from the colons of healthy and UC patients and found several distinct populations of CD8+ T cells defining functionally distinct types and states during active disease.
By examining a single cell’s unique T cell receptor, they were able to infer the life course of T cells in a healthy state and ulcerative colitis. They found during active disease, colonic resident memory populations of T cells can expand into differentiate into pro-inflammatory effector cells and then more terminally differentiated T cells possessing immunoregulatory features. Furthermore, they uncover potential pathways by which the differing T cell types might injure the epithelial barrier in active ulcerative colitis.
Author Dr Agne Antanaviciute said: “An imbalance between inflammatory effectors and immunoregulatory T cells may facilitate tissue destruction that manifests as ulcerative colitis.”
Professor Alison Simmons of the MRC-WIMM said: “The findings provide evidence for a role of CD8 T cells in IBD and add to the single-cell resource created in our own lab and internationally that acts as a platform for the development of improved treatments for the condition.”