Published on December 12, 2025
A Spatial Atlas of Human Gastrointestinal Acute GVHD Reveals Epithelial and Immune Dynamics Underlying Disease Pathophysiology
by Alex Kadhim
Researchers at the Weizmann Institute of Science have generated a high-resolution spatial atlas of the human gastrointestinal tract in acute graft-versus-host disease (aGVHD), revealing epithelial disruption and unexpected immune cell patterns that reshape how the disease is understood. The study, published in Science Translational Medicine, found that aGVHD involves far more than donor T-cell–mediated tissue damage. Instead, widespread epithelial remodeling, fibrosis, and the surprising persistence of host-derived T cells and plasma cells contribute to disease biology, offering a more nuanced view of why patients experience such variable clinical outcomes.
aGVHD remains one of the most severe and unpredictable complications of allogeneic stem cell transplantation. Although traditionally attributed to donor T-cell attack on host tissues, this model has never fully explained the broad clinical spectrum or why some patients exhibit profound gut dysfunction while others do not. Existing approaches have also lacked the spatial resolution needed to study epithelial and immune interactions directly in human tissue. In this study, the authors used multiplexed imaging of 40 proteins across 59 biopsies from patients with gastrointestinal aGVHD and 18 healthy controls to map epithelial, stromal, and immune organization at single-cell resolution. This allowed them to examine structural changes in crypts, regional immune composition, fibrosis, and the balance of host versus donor immune cells over time after transplantation.
Across 77 total biopsies, healthy duodenum displayed highly stereotyped epithelial and immune zonation, whereas aGVHD tissue showed increased fibrosis, crypt distortion, loss of Paneth cells, and accumulation of endocrine cells. IgA-secreting plasma cells were markedly reduced, and immune rewiring varied across patients: some exhibited strong CD8 T-cell enrichment, while others showed noncanonical increases in macrophages or neutrophils. Immune composition correlated with time post-transplant, and host-derived T cells and plasma cells often remained dominant long after engraftment. These findings highlight that aGVHD arises from multiple interacting epithelial and immune processes rather than a single donor T-cell–driven mechanism, providing a foundational spatial resource that could guide biomarker development and more targeted therapeutic strategies.
Reference:
Azulay N, Milo I, Bussi Y, et al. A spatial atlas of human gastrointestinal acute GVHD reveals epithelial and immune dynamics underlying disease pathophysiology. Sci Transl Med. 2025;17(823):eadu6032.
http://doi.org/10.1126/scitranslmed.adu6032
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