Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Parvathi Ranganathan1,
  2. Catherine E.A. Heaphy1,
  3. Stefan Costinean2,
  4. Nicole Stauffer1,
  5. Caroline Na1,
  6. Mehdi Hamadani3,
  7. Ramasamy Santhanam2,
  8. Charlene Mao1,
  9. Patricia A. Taylor4,
  10. Sukhinder Sandhu2,
  11. Gang He5,
  12. Arwa Shana'ah6,
  13. Gerard J. Nuovo6,
  14. Susanna Obad7,
  15. Oliver Broom7,
  16. Sakari Kauppinen8,
  17. John C. Byrd1,
  18. Michael Caligiuri1,
  19. Danilo Perrotti2,
  20. Gregg A. Hadley9,
  21. Guido Marcucci1,
  22. Steven M. Devine1,
  23. Bruce R. Blazar4,
  24. Carlo M. Croce2, and
  25. Ramiro Garzon1,*
  1. 1 Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States;
  2. 2 Department of Molecular Virology, Immunology and Molecular Genetics, The Ohio State University, Columbus, OH, United States;
  3. 3 Divison of Hematology and Oncology, Department of Medicine, West Virginia University, Morgantown, WV, United States;
  4. 4 Masonic Cancer Center and the Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, United States;
  5. 5 Department of Pathology, University of Manitoba, Winnipeg, MB, Canada;
  6. 6 Department of Pathology, The Ohio State University, Columbus, OH, United States;
  7. 7 Santaris Pharma, Horsholm, Denmark;
  8. 8 Copenhagen Institute of Technology, Aalborg University, Ballerup, Denmark;
  9. 9 Division of Transplantation, Department of Surgery, The Ohio State University, Columbus, OH, United States
  1. * Corresponding author; email: ramiro.garzon{at}osumc.edu

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 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.