MicroRNA-181a, a potential diagnosis marker, alleviates acute graft versus host disease by regulating IFN-γ production.
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.
American journal of hematology
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; and Xu, Kailin, "MicroRNA-181a, a potential diagnosis marker, alleviates acute graft versus host disease by regulating IFN-γ production." (2015). PCOM Scholarly Papers. 1377.