美国拉霍亚免疫学研究所Pandurangan Vijayanand和Mitchell Kronenberg小组的研究发现，干细胞样T细胞与人类溃疡性结肠炎（UC）的发病有关。相关论文发表在2024年6月19日出版的《自然-免疫学》杂志上。

为了揭示T细胞在溃疡性结肠炎发病中的作用，研究人员分析了从UC患者和对照组中分离的结肠T细胞。

研究人员发现了结肠CD4⁺和CD8⁺ T淋巴细胞亚群，它们的基因表达谱与干细胞样祖细胞相似。与来自同一患者的非炎症区域相比，炎症区域的干细胞样T细胞数目有所增加。

此外，TCR序列分析表明干细胞样T细胞与促炎症T细胞之间存在克隆关系，表明它们参与维持诱导炎症的效应因子。研究人员利用小鼠过继转移结肠炎模型证明，CD4⁺ T细胞缺乏BCL-6或TCF1（促进T细胞干细胞性的转录因子），结肠T细胞减少，致病性降低。该研究结果确立了干细胞样T细胞群与UC发病之间存在密切联系，表明靶向这一细胞群可能会改善临床治疗效果。

附：英文原文

Title: Stem-like T cells are associated with the pathogenesis of ulcerative colitis in humans

Author: Li, Yingcong, Ramrez-Sustegui, Ciro, Harris, Richard, Castaeda-Castro, Francisco Emmanuel, Ascui, Gabriel, Prez-Jeldres, Tamara, Diaz, Alejandro, Morong, Carla, Giles, Daniel A., Chai, Jiani, Seumois, Gregory, Sanchez-Elsner, Tilman, Cummings, Fraser, Kronenberg, Mitchell, Vijayanand, Pandurangan

Issue&Volume: 2024-06-19

Abstract: 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.

DOI: 10.1038/s41590-024-01860-7

Source: https://www.nature.com/articles/s41590-024-01860-7