title: miR-181a Expression in Donor T Cells Modulates Graft-versus-Host Disease after Allogeneic Bone Marrow Transplantation.
abstract: Because miR-181a has been described to alter T cell activation, we hypothesized that manipulation of miR-181a expression in donor T cells may alter acute graft-versus-host disease (aGvHD) after allogeneic bone marrow transplantation (BMT). We therefore analyzed the impact of enhanced and reduced miR-181a expression in donor T cells on aGvHD induction by lentiviral gene transfer into primary T cells and using miR-181a/b-1(-/-) T cells, respectively. BMT-recipient mice receiving donor T cells with enhanced miR-181a expression showed no signs of aGvHD and survived for the time of follow-up, whereas T cells lacking miR-181a/b-1 accelerated aGvHD. In line with these data, analysis of donor T cells in blood, secondary lymphoid organs, and target organs of aGvHD after BMT showed significantly reduced numbers of miR-181a-transduced T cells, as compared with controls. In addition, expansion of activated T cells with enhanced miR-181a expression was reduced in vitro and in vivo. We further show that anti-apoptotic BCL-2 protein expression is reduced in murine and human T cells upon overexpression of miR-181a, suggesting that regulation of BCL-2-expression by miR-181a may contribute to altered alloreactivity of T cells in aGvHD. These data indicate that proteins regulated by miR-181a may be therapeutic targets for aGvHD prevention.
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, D-30625 Hannover, Germany; and Institute of Immunology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Chun-Wei
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, D-30625 Hannover, Germany; and.
authors.forename: Katharina
authors.initials: K
authors.lastname: Wohlan
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, D-30625 Hannover, Germany; and.
authors.forename: Iris
authors.initials: I
authors.lastname: Dallmann
authors.affiliation: Institute of Immunology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Reinhold
authors.initials: R
authors.lastname: Förster
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, D-30625 Hannover, Germany; and.
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.affiliation: Institute of Immunology, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Andreas
authors.identifier: 0000-0001-7873-7334
authors.initials: A
authors.lastname: Krueger
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, D-30625 Hannover, Germany; and M.Scherr@t-online.de Eder.Matthias@mh-hannover.de Koenecke.Christian@mh-hannover.de.
authors.forename: Michaela
authors.initials: M
authors.lastname: Scherr
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, D-30625 Hannover, Germany; and M.Scherr@t-online.de Eder.Matthias@mh-hannover.de Koenecke.Christian@mh-hannover.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Eder
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, D-30625 Hannover, Germany; and Institute of Immunology, Hannover Medical School, D-30625 Hannover, Germany M.Scherr@t-online.de Eder.Matthias@mh-hannover.de Koenecke.Christian@mh-hannover.de.
authors.forename: Christian
authors.identifier: 0000-0001-7025-1735
authors.initials: C
authors.lastname: Koenecke
mesh_terms: D000208:Acute Disease; D000818:Animals; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D002478:Cells, Cultured; D006086:Graft vs Host Disease / Q000276:immunology* / Q000517:prevention & control; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology* / Q000637:transplantation; D014184:Transplantation, Homologous
chemical_list: D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; C529100:mirn181 microRNA, mouse