Single-cell Profiling Reveals Diverse γδ T Cell Subsets in Ulcerative Colitis

γδ T cells maintain intestinal immune homeostasis, but their contributions to human ulcerative colitis (UC) are poorly understood. We characterized γδ T cells in intestinal biopsies obtained from patients with UC and healthy donors using single-cell RNA sequencing, T cell receptor profiling, and mass cytometry. UC reduced CD103+Vγ4Vδ1+ intraepithelial γδ lymphocytes (γδ IELs) and increased γδ T cell subsets with stem-like phenotypes expressing T cell factor-1 (TCF-1) and programmed cell death receptor 1 (PD-1), or effector-like phenotypes expressing granzyme B, perforin, and T-box expressed in T cells (T-bet). γδ T cell composition changes in UC correlated with decreased expression of epithelial BTNL3 and BTNL8 and increased BTN3A1 and BTN3A3 , suggesting altered recruitment and activation . Clinical improvement recovered γδ IELs and reduced inflammation-associated subsets. Inflammation-associated changes were observed in peripheral blood γδ T cells. Thus, distinct γδ T cell subsets in different niches exert protective or pathogenic functions in UC.