Research ArticleTransplantation

Zbtb7a induction in alveolar macrophages is implicated in anti-HLA–mediated lung allograft rejection

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Science Translational Medicine  12 Jul 2017:
Vol. 9, Issue 398, eaal1243
DOI: 10.1126/scitranslmed.aal1243

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Curbing culprits of chronic rejection

De novo donor-specific antibodies generated after organ transplantation can lead to chronic rejection, and Nayak et al. sought to understand the mechanisms leading to production of these antibodies in lung transplantation. Using mouse models and data from human patients, they identified expression of the transcription factor Zbtb7a in alveolar macrophages as a crucial mediator. Patients eventually diagnosed with chronic rejection had higher expression of this transcription factor early on. Preventing macrophages from expressing Zbtb7a ameliorated models of obliterative airway disease and prevented chronic rejection of lung transplants in mice. Interrupting macrophage presentation of donor antigens may be a solution to prevent generation of these destructive antibodies and the ensuing chronic rejection.