GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE284nnn/GSE284015/primaryOK200TranscriptomicsHomo sapiens OtherExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE284015GEOGSEfalseGZMK-expressing tissue-resident memory CD8+ T cells mediate human intestinal acute graft-versus-host diseaseTissue-resident memory T cells (TRM) have recently emerged as crucial cellular players for murine acute graft-versus-host disease (aGVHD) development. However, the role of distinct subsets of CD8+TRM cells in human intestinal aGVHD is not well known yet. Herein,we combined multiplex immunohistochemical staining with single-cell RNA sequencing to elucidate the differentiation trajectory, lineage commitment, clonal expansion and functional properties of distinct CD8+TRM cell subsets in human intestinal aGVHD. We revealed seven functionally distinct CD8+TRM subsets and innovatively uncovered a significant GZMK+CD8+TRM subset. GZMK+CD8+TRM subset mediated human intestinal aGVHD by exhibiting enhanced clonal expansion, IFN signaling pathway-associated proinflammatory, and lineage bifurcation differentiation properties. High GZMK+CD8+TRM subset infiltration is correlated with human intestinal aGVHD severity and poor prognosis. Therefore, we demonstrated that human intestinal aGVHD is in good part mediated by pivotal GZMK+CD8+TRM subset. Targeting key CD8+TRM cell subsets could be a new treatment approach in the human intestinal aGVHD.2026/05/06GSE284015GSM8676180GSM9060920GSM8676184GSM8676183GSM8676182GSM8676181GSM8676188GSM8676187GSM8676186GSM8676185GSM8676189GSM8676191GSM8676190GSM8676195GSM8676194GSM8676193GSM8676192GSM9060919GSM8676177GSM8676176GSM8676197GSM8676175GSM8676196GSM8676174GSM8676179GSM867617824676284015Homo sapiens