Related Experiment Video
Updated: Sep 16, 2025
Murine Full-thickness Skin Transplantation
Published on: January 2, 2017
Hypomethylating therapy mitigates acute allograft rejection in a murine lung transplant model
Kristine M Yarnoff1, William N Daccarett-Bojanini1, Andres F Villabona-Rueda2
1Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institution, Baltimore, MD, United States.
Introduction:
Acute cellular rejection of transplanted lung allografts involves activated cytotoxic T cells and reduced Regulatory T (Treg) cell function. Calcineurin inhibitors, the cornerstone of immunosuppressive regimens, suppress T cell cytotoxicity but inhibit Treg proliferation. The DNA hypomethylating agent decitabine (DAC) can abrogate T cell cytotoxicity while stimulating Treg proliferation.
Methods:
We sought to determine the effects of DAC treatment in a murine MHC-mismatched orthotopic lung transplant model.
Results:
Rescue treatment with DAC maintains lung allograft gross and histologic integrity with a reduction in cytotoxic T cell responses. CD4+FoxP3+ T cell depletion in Foxp3DTR mice exacerbated rejection lung injury compared to CD4+FoxP3+ T cell sufficient mice and failed to abolish the protective effect of DAC in this model. The protective effect of DAC was associated with a reduction in cytokine production from host T-cells.
Discussion:
Decitabine could offer a new line of treatment for acute lung allograft rejection, in part via its effects on Tregs.
