Single-cell profiling reveals diverse γδ T cell subsets in ulcerative colitis

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Abstract
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 + γδ intraepithelial lymphocytes (γδ IELs) and increased γδ T cell subsets with stemlike phenotypes expressing TCF-1 (T cell factor 1) and PD-1 (programmed cell death receptor 1) or effector-like phenotypes expressing granzyme B, perforin, and T-bet in the lamina propria. 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.
Funding Information
  • Deutsche Forschungsgemeinschaft (MA 8128/1-1)
  • Deutsche Forschungsgemeinschaft (256073931)
  • Deutsche Forschungsgemeinschaft (491676693)
  • Deutsche Forschungsgemeinschaft (HO 5836/2-1)
  • Deutsche Forschungsgemeinschaft (322977937/GRK2344)
  • Deutsche Forschungsgemeinschaft (518316185)
  • Deutsche Forschungsgemeinschaft (MA 8128/1-1)
  • Deutsche Forschungsgemeinschaft (SFB 1160)
  • Deutsche Forschungsgemeinschaft (TRR 359)
  • Deutsche Forschungsgemeinschaft (HO 5836/2-1)
  • Deutsche Forschungsgemeinschaft (ID 491676693)
  • Deutsche Forschungsgemeinschaft (322977937/GRK2344)
  • Deutsche Forschungsgemeinschaft (413517907)
  • Deutsche Forschungsgemeinschaft (450392965)

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