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

Parvathi Ranganathan, Catherine E A Heaphy, Stefan Costinean, Nicole Stauffer, Caroline Na, Mehdi Hamadani, Ramasamy Santhanam, Charlene Mao, Patricia A. Taylor, Sukhinder Sandhu, Gang He, Arwa Shana'ah, Gerard J. Nuovo, Alessandro Lagana, Luciano Cascione, Susanna Obad, Oliver Broom, Sakari Kauppinen, John C. Byrd, Michael CaligiuriDanilo Perrotti, Gregg A. Hadley, Guido Marcucci, Steven M. Devine, Bruce R. Blazar, Carlo M. Croce, Ramiro Garzon

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4786-4797
Number of pages12
JournalBlood
Volume119
Issue number20
DOIs
StatePublished - May 17 2012

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