Enforced gut homing of murine regulatory T cells reduces early graft-versus-host disease severity

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.

Automated summary

Damage to the gastrointestinal tract plays a significant role in the severity and perpetuation of graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. In preclinical models and clinical trials, infusing high numbers of regulatory T cells has been shown to reduce the incidence of graft-versus-host disease. Transferring ex vivo expanded regulatory T cells overexpressing G protein-coupled receptor 15 or C-C motif chemokine receptor 9, specific homing receptors for colon or small intestine respectively, can lessen the severity of graft-versus-host disease in mice.