title: MicroRNA-181a, a potential diagnosis marker, alleviates acute graft versus host disease by regulating IFN-γ production.
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.
authors.affiliation: The first clinical medical college of Nanjing Medical University, Nanjing, China.|The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sang
authors.affiliation: The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Philadelphia College of Osteopathic Medicine, USA.
authors.forename: Dianzheng
authors.initials: D
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Sun
authors.affiliation: The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Mingshan
authors.initials: M
authors.lastname: Niu
authors.affiliation: Department of Medicine, Penn State Hershey Cancer Institute, Hershey, Pennsylvania, USA.
authors.forename: Xiaoshen
authors.initials: X
authors.lastname: Sun
authors.affiliation: The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Zhou
authors.affiliation: The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Zeng
authors.affiliation: The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Pan
authors.affiliation: The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Yan
authors.affiliation: The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.affiliation: The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Wu
authors.affiliation: The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Cao
authors.affiliation: The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.affiliation: The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Depeng
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Medicine, University of Virginia Cancer Center, Virginia, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Loughran
authors.affiliation: The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D011379:Prognosis; D015398:Signal Transduction; D016019:Survival Analysis; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
chemical_list: D015415:Biomarkers; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; C529100:mirn181 microRNA, mouse; D007371:Interferon-gamma