MicroRNA-155 regulates T cell proliferation through targeting GSK3β in cardiac allograft rejection in a murine transplantation model

• miR-155 is expressed in T lymphocytes during acute cardiac rejection.
• GSK3β is a novel direct target of miR-155 in cardiac allograft rejection.
• miR-155 promotes T-cell proliferation by targeting GSK3β in vitro.
• miR-155 may play role in the pathogenesis of allograft rejection after cardiac transplantation.

Here we investigated the activity and regulation of miR-155 during cardiac allograft rejection (AR), and to examine the feasibility of using miR-155 as a biomarker of graft status. Expression of miR-155 in graft-infiltrating lymphocytes (GIL), T cells isolated from spleen (TFS), and lymphocytes separated from blood (LFB) was significantly increased during cardiac AR while GSK3β was downregulated in GIL and TFS. Inhibition of miR-155 impaired lymphocyte proliferation and enhanced the expression of GSK3β. Moreover, pharmacological inactivation of GSK3β resulted in rescue of the proliferative capability of T cells pretreated with a miR-155 inhibitor. Luciferase reporter assay confirmed that miR-155 interacted with the 3′-untranslated region (UTR) of GSK3β directly. In particular, the miR-155 in LFB can distinguish recipients with AR from syngeneic controls from POD 3 and later. The present study provides a better understanding of the pathophysiological process underlying cardiac AR progression.