Stem-like T cells are associated with the pathogenesis of ulcerative colitis in humans [scRNAseq_Human]

To understand the role of T cells in the pathogenesis of ulcerative colitis (UC), we analyzed colonic T cells isolated from UC patients and controls. We identified colonic CD4+ and CD8+ 32 T lymphocyte subsets with gene expression profiles resembling stem-like progenitors, previously reported in animal models of diabetes and other contexts. Stem-like T cells were increased in inflamed areas compared to non-inflamed regions from the same patients. Furthermore, TCR sequence analysis indicated stem-like T cells were clonally related to pro-inflammatory T cells, suggesting their involvement in sustaining effectors that drive inflammation. Using an adoptive transfer colitis model, we demonstrated that CD4+ 38 T cells deficient in BCL-6, a transcription factor promoting T cell stemness, had decreased colon T cells, reduced TH17 cells, and diminished pathogenicity. Our results establish a strong association between stem-like T cell populations and UC pathogenesis, highlighting the potential of targeting this population to improve clinical outcomes.