MicroRNA-181a, a potential diagnosis marker, alleviates acute graft versus host disease by regulating IFN-γ production

Am J Hematol. 2015 Nov;90(11):998-1007. doi: 10.1002/ajh.24136. Epub 2015 Oct 8.

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a valuable therapeutic strategy for a wide variety of diseases. Acute graft-versus-host disease (aGVHD) is a major complication in up to 75% of allo-HSCT. The absence of a reliable predicative marker for aGVHD onset prevents preemptive treatment and impedes widespread and successful application of this therapy. In this study we found that after allo-HSCT, the levels of miR-181a were reduced significantly prior to the onset of aGVHD. More importantly, the degree of its reduction correlated with the severity of aGVHD. Mechanistically, miR-181a affects the function of T lymphocytes by down-regulating IFN-γ in a dose-dependent manner. Meanwhile, we confirmed that miR-181a can effectively preserve the anti-leukemic effect in vitro. Using a murine allo-HSCT model, we demonstrated that murine miR-181b, the human miR-181a homolog, served as an effective predictor of aGVHD. Moreover, expression of this microRNA ameliorated the severity of aGVHD. Collectively, these results show that the level of miR-181a may serve as a reliable marker for the diagnosis and prognosis the onset of aGVHD. Am. J. Hematol. 90:998-1007, 2015. © 2015 Wiley Periodicals, Inc.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Animals
  • Biomarkers / metabolism
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Graft vs Host Disease / diagnosis*
  • Graft vs Host Disease / genetics*
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / mortality
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Interferon-gamma / genetics*
  • Interferon-gamma / immunology
  • Male
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • MicroRNAs / immunology
  • Middle Aged
  • Prognosis
  • Signal Transduction
  • Survival Analysis
  • Transplantation, Homologous
  • Whole-Body Irradiation

Substances

  • Biomarkers
  • MIrn181 microRNA, human
  • MicroRNAs
  • mirn181 microRNA, mouse
  • Interferon-gamma