MicroRNA-150 negatively regulates the function of CD4+ T cells through AKT3/Bim signaling pathway

Document Type

Article

Publication Date

2016

Abstract

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.

Publication Title

Cellular immunology

Comments

This article was published in Cellular immunology.

The published version is available at /http://dx.doi.org/10.1016/j.cellimm.2016.05.007.

Copyright © 2016 Elsevier .

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