ORIGINAL RESEARCH article
Front. Transplant.
Sec. Transplantation Immunology
This article is part of the Research TopicAdvances in Transplantation: From New Actors and Pathways of Rejection to Engineering OrgansView all articles
The Role of Macrophages in the Mitigation by Decitabine of Acute Allograft Rejection
Provisionally accepted
- Johns Hopkins University, Baltimore, United States
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We have recently shown that the DNA hypomethylating agent decitabine (DAC) rescues lung allografts from acute rejection. This involves a mechanism that is dependent on host CD4+FoxP3+ T cells for maximal benefit. DAC treatment also reduces host T cell IFN- production. We therefore hypothesized that DAC may also reduce host macrophage activation. Our objective was to determine if an effect on macrophages contributes to the beneficial effects of DAC in transplantation. In murine orthotopic lung transplant, hosts were treated post-op day 3-8 with Clodronate (n=5), DAC (n = 9), or DMSO (n = 11). Partial macrophage depletion (clodronate) improves allograft gross and histologic integrity. DAC-mediated allograft rescue was associated with reduced host macrophage recruitment into allograft airways, reduced activation of recruited macrophages, and regeneration of donor resident alveolar macrophages. These finding suggest that infiltrating host macrophages promote allograft rejection. They also suggest that donor alveolar health is indicative and/or promoting of allograft tolerance.
Keywords: Lung Transplantation, acute rejection, macrophage, decitabine, Immune Tolerance
Received: 12 Oct 2025; Accepted: 18 Nov 2025.
Copyright: © 2025 Daccarett-Bojanini, Sollmann, Yarnoff, Heller and Dodd-o. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Johns Dodd-o, jdoddo@jhmi.edu
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