title: MicroRNA-150 negatively regulates the function of CD4(+) T cells through AKT3/Bim signaling pathway.
abstract: Donor-derived CD4(+) T lymphocytes are the major effector cells directly involved in the development of graft-versus-host disease (GVHD). As a negative regulator of immune cell differentiation and development, microRNA-150 (miR-150) induces immunological tolerance in CD4(+) T cells after transplantation. However, the specific mechanisms have not been fully elucidated. In this study, we demonstrated that miR-150 is capable of not only inhibiting proliferation and activation of CD4(+) T cells but also promoting apoptosis. Mechanistically, miR-150 targets v-akt murine thymoma viral oncogene homolog 3 (AKT3), and subsequently downregulates B-cell lymphoma 2 (Bcl-2) interacting mediator of cell death (BIM). We have also demonstrated that re-expression of AKT3 reversed miR-150-mediated inhibition of CD4(+) T lymphocyte development. Therefore, we conclude that miR-150 negatively regulates CD4(+) T cell function by inhibiting the AKT3/BIM signaling pathway. These findings also suggest that manipulating the levels of miRNA-150 could be a valuable strategy in prevention and/or treatment of acute graft-versus-host disease.
authors.affiliation: Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical University, Jiangsu Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sang
authors.affiliation: Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical University, Jiangsu Province, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of hematology, Huaibei Miners General Hospital, Anhui Province, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, USA.
authors.forename: Dianzheng
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical University, Jiangsu Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical University, Jiangsu Province, China.
authors.forename: Linyan
authors.initials: L
authors.lastname: Xu
authors.affiliation: Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical University, Jiangsu Province, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical University, Jiangsu Province, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Wei
authors.affiliation: Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical University, Jiangsu Province, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Pan
authors.affiliation: Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical University, Jiangsu Province, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Yan
authors.affiliation: Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical University, Jiangsu Province, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical University, Jiangsu Province, China.
authors.forename: Zhiling
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical University, Jiangsu Province, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Medicine, University of Virginia Cancer Center, VA, USA. Electronic address: tploughran@virginia.edu.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Loughran
authors.affiliation: Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; The Key Laboratory of Transplantation Immunity, Affiliated Hospital of Xuzhou Medical University, Jiangsu Province, China. Electronic address: kailinxu616@126.com.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
mesh_terms: D017209:Apoptosis / Q000235:genetics; D000072224:Bcl-2-Like Protein 11 / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D006086:Graft vs Host Disease / Q000517:prevention & control*; D057809:HEK293 Cells; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008213:Lymphocyte Activation; D035683:MicroRNAs / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D014184:Transplantation, Homologous
chemical_list: D000072224:Bcl-2-Like Protein 11; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; C000606776:Bcl2l11 protein, mouse; C533097:MIR150, human; C491754:AKT3 protein, human
keywords: AKT3; Apoptosis; Bim; CD4(+) T cells; miR-150