Regulation of acute graft-versus-host disease by microRNA-155

P Ranganathan, CEA Heaphy… - Blood, The Journal …, 2012 - ashpublications.org
P Ranganathan, CEA Heaphy, S Costinean, N Stauffer, C Na, M Hamadani, R Santhanam…
Blood, The Journal of the American Society of Hematology, 2012ashpublications.org
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 microRNA-
155 (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 after alloHSCT. Mice receiving miR-155 …
Abstract
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 microRNA-155 (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 after alloHSCT. Mice receiving miR-155–deficient donor lymphocytes had markedly reduced lethal aGVHD, whereas lethal aGVHD developed rapidly in mice recipients of miR-155 overexpressing T cells. Blocking miR-155 expression using a synthetic anti–miR-155 after alloHSCT decreased aGVHD severity and prolonged survival in mice. Finally, miR-155 up-regulation was shown in specimens from patients with pathologic 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.
ashpublications.org