Acute graft-versus-host disease (aGVHD) remains a major complication of allogeneic hematopoietic stem cell transplant (alloHSCT), underscoring the need to further elucidate its mechanisms and develop novel treatments. Based on recent observations that miR-155 is up-regulated during T cell activation, we hypothesized that miR-155 is involved in the modulation of aGVHD. Here we show that miR-155 expression was up-regulated in T cells from mice developing aGVHD following alloHSCT. Mice receiving miR-155 deficient donor lymphocytes had markedly reduced lethal aGVHD, while lethal aGVHD developed rapidly in mice recipients of miR-155 over-expressing T cells. Blocking miR-155 expression using a synthetic antimiR-155 following alloHSCT decreased aGVHD severity and prolonged survival in mice. Finally, miR-155 up-regulation was shown in specimens from patients with pathological evidence of intestinal aGVHD. Altogether our data indicate a role for miR-155 in the regulation of GVHD, and point to miR-155 as a novel target for therapeutic intervention in this disease.
- Submitted October 21, 2011.
- Accepted March 1, 2012.
- Copyright © 2005 American Society of Hematology