L Mayer, Jakob Arnold, Felix Roettele, Nadine Reuter, Ajinkya Pattekar, Takuya Ohtani, Mariana Messias Ribeiro, Rebecca Siwicki, Kerstin Bruder, David Obwegs, Elin Stahl, Sarah Buechel, Natascha Roehlen, Julia Kolter, Zohreh Mansoori Moghadam, Ahmed Alaswad, Zhibek Zhumalidova, Guang Li, Xinjuan Liu, Yang Li, Amit Singh, José Villacorta Hidalgo, M Paraskevopoulou, Vijay Yajnik, Julius Juaréz, Yue Ren, Hui Li, E. John Wherry, James D. Lewis, Gary D. Wu, Meenakshi Bewtra, Vesselin T. Tomov, R Thimme, Bertram Bengsch, Peter Hasselblatt, Simone Picelli, Maike Hofmann, Sagar
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.