Abstract
Damage to the gastrointestinal tract following allogeneic hematopoietic stem cell transplantation is a significant contributor to the severity and perpetuation of graft-versus-host disease. In preclinical models and clinical trials, we showed that infusing high numbers of regulatory T cells reduces graft-versus-host disease incidence. Despite no change in in vitro suppressive function, transfer of ex vivo expanded regulatory T cells transduced to overexpress G protein–coupled receptor 15 or C-C motif chemokine receptor 9, specific homing receptors for colon or small intestine, respectively, lessened graft-versus-host disease severity in mice. Increased regulatory T cell frequency and retention within the gastrointestinal tissues of mice that received gut homing T cells correlated with lower inflammation and gut damage early post-transplant, decreased graft-versus-host disease severity, and prolonged survival compared with those receiving control transduced regulatory T cells. These data provide evidence that enforced targeting of ex vivo expanded regulatory T cells to the gastrointestinal tract diminishes gut injury and is associated with decreased graft-versus-host disease severity.
Original language | English (US) |
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Pages (from-to) | 1102-1115 |
Number of pages | 14 |
Journal | American Journal of Transplantation |
Volume | 23 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2023 |
Bibliographical note
Publisher Copyright:© 2023 American Society of Transplantation & American Society of Transplant Surgeons
Keywords
- CCR9
- GPR15
- GVHD
- lymphocyte homing
- regulatory T cell