%0 Journal Article
%T Stem-like T cells are associated with the pathogenesis of ulcerative colitis in humans.
%A Li Y
%A Ramírez-Suástegui C
%A Harris R
%A Castañeda-Castro FE
%A Ascui G
%A Pérez-Jeldres T
%A Diaz A
%A Morong C
%A Giles DA
%A Chai J
%A Seumois G
%A Sanchez-Elsner T
%A Cummings F
%A Kronenberg M
%A Vijayanand P
%J Nat Immunol
%V 25
%N 7
%D 2024 Jul 19
%M 38898157
%F 31.25
%R 10.1038/s41590-024-01860-7
%X To understand the role of T cells in the pathogenesis of ulcerative colitis (UC), we analyzed colonic T cells isolated from patients with UC and controls. Here we identified colonic CD4+ and CD8+ T lymphocyte subsets with gene expression profiles resembling stem-like progenitors, previously reported in several mouse models of autoimmune disease. 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 proinflammatory T cells, suggesting their involvement in sustaining effectors that drive inflammation. Using an adoptive transfer colitis model in mice, we demonstrated that CD4+ T cells deficient in either BCL-6 or TCF1, transcription factors that promote T cell stemness, had decreased colon T 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.