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

• Published in: American journal of hematology Vol. 90; no. 11; pp. 998 - 1007
• Main Authors: Sang, Wei, Zhang, Cong, Zhang, Dianzheng, Wang, Ying, Sun, Cai, Niu, Mingshan, Sun, Xiaoshen, Zhou, Cui, Zeng, Lingyu, Pan, Bin, Chen, Wei, Yan, Dongmei, Zhu, Feng, Wu, Qingyun, Cao, Jiang, Zhao, Kai, Chen, Chong, Li, Zhenyu, Li, Depeng, Loughran, Thomas P., Xu, Kailin
• Format: Journal Article
• Language: English
• Published: United States 01.11.2015
• Subjects: 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
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/ajh.24136

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.