Single-Cell Transcriptional Survey of Murine Intestinal Graft-versus-Host Disease

Acute Graft-versus-host disease (aGVHD) is a major cause of mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The intestinal epithelium plays a crucial role in digestive and barrier function, as well as microbiome and immune balance, and additionally it is one of the primary targets of aGVHD. Despite extensive research on aGVHD mechanisms, a comprehensive understanding of intestinal damage and repair in this context remains elusive. In this study, a longitudinal analysis was conducted on the cellular composition of the small intestine in a murine model of aGVHD. The results showed that enterocyte deficiency and impaired absorptive capacity were significant aspects of disease progression. The immune profiles also underwent significant changes after transplantation. Particularly, pathogenic alphabeta T cells in aGVHD exhibited enhanced proliferation, differentiation, effector functions, and resistance to terminal exhaustion. Additionally, fibroblasts were significantly involved in cell communication within the intestine during aGVHD, where they disrupt the normal regulation of immunity and epithelial regeneration. Overall, these findings indicated that aGVHD is a complex condition influenced by various factors beyond just the dysregulated immune system.