Browsing by Author "Harris, Richard"

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    Stem-like T cells are associated with the pathogenesis of ulcerative colitis in humans
    (2024) Li, Yingcong; Ramirez-Suastegui, Ciro; Harris, Richard; Castaneda-Castro, Francisco Emmanuel; Ascui, Gabriel; Perez-Jeldres, Tamara; Diaz, Alejandro; Morong, Carla; Giles, Daniel A.; Chai, Jiani; Seumois, Gregory; Sanchez-Elsner, Tilman; Cummings, Fraser; Kronenberg, Mitchell; Vijayanand, Pandurangan
    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.