miR-625-3p is upregulated in CD8+ T cells during early immune reconstitution after allogeneic stem cell transplantation
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Colleges, School and Institutes
- Dept. of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
- Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany.
- Department of Histopathology, Royal Brompton and Harefield NHS Foundation Trust and National heart and Lung Institute, Imperial College, London, United Kingdom.
- Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Alloreactive CD8+ T-cells mediate the curative graft-versus-leukaemia effect, the anti-viral immunity and graft-versus-host-disease (GvHD) after allogeneic stem cell transplantation (SCT). Thus, immune reconstitution with CD8+ T-cells is critical for the outcome of patients after allogeneic SCT. Certain miRNAs such as miR-146a or miR-155 play an important role in the regulation of post-transplant immunity in mice. While some miRNAs e.g. miR-423 or miR-155 are regulated in plasma or full blood during acute GvHD also in man, the relevance and expression profile of miRNAs in T-cells after allogeneic SCT is unknown. miR-625-3p has recently been described to be overexpressed in colorectal malignancies where it promotes migration, invasion and apoptosis resistance. Since similar regulative functions in cancer and T-cells have been described for an increasing number of miRNAs, we assumed a role for the cancer-related miR-625-3p also in T-cells. Here, we studied miR-625-3p expression selectively in CD8+ T-cells both in vitro and during immune reconstitution after allogeneic SCT in man. T-cell receptor stimulation lead to miR-625-3p upregulation in human CD8+ T-cells in vitro. Maintenance of elevated miR-625-3p expression levels was dependent on ongoing T-cell proliferation and was abrogated by withdrawal of interleukin 2 or the mTOR inhibitor rapamycin. Finally, miR-625-3p expression was analyzed in human CD8+ T-cells purified from 137 peripheral blood samples longitudinally collected from 74 patients after allogeneic SCT. miR-625-3p expression was upregulated on day 25 and on day 45, i.e. during the early phase of CD8+ T-cell reconstitution after allogeneic SCT and subsequently declined with completion of CD8+ T-cell reconstitution until day 150. In conclusion, this study has shown for the first time that miR-625-3p is regulated in CD8+ T-cells during proliferation in vitro and during early immune reconstitution after allogeneic SCT in vivo. These results warrant further studies to identify the targets and function of miR-625-3p in CD8+ T-cells and to analyze its predictive value for an effective immune reconstitution.
|Publication status||Published - 30 Aug 2017|
- CD8-Positive T-Lymphocytes/immunology, Cell Proliferation/genetics, Female, Graft vs Host Disease/genetics, Humans, Lymphocyte Activation/genetics, Male, MicroRNAs/genetics, Middle Aged, Receptors, Antigen, T-Cell/genetics, Reverse Transcriptase Polymerase Chain Reaction, Stem Cell Transplantation/methods, Time Factors, Transcriptional Activation, Transplantation, Homologous, Up-Regulation