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- W2768350982 abstract "Introduction The circadian clock regulates murine immune responses by time of day, partly through the clock protein REVERBα, resulting in altered mortality after infection. The mechanisms regulating time of day differences are poorly understood in humans, where performing circadian studies presents a number of challenges. Lung transplantation, which is performed at any time of day to minimise organ ischaemic time, is an ideal model to study circadian effects on human immune responses. Methods Primary graft dysfunction (PGD) incidence after lung transplantation was examined for an eight year retrospective (2004–2012) cohort (n=563) in one centre. Patients were excluded, a priori, if they had significant intra-operative complications, had a previous lung transplant, or if the donor lung had undergone ex-vivo perfusion. Circadian factors were also studied using PER2::Luc and REVERBα-/- mice and by pharmacological targeting of the circadian clock in primary alveolar macrophages from lung transplant recipients. Results The incidence of PGD grades 2/3 at 24 hours was temporarily elevated when organs were reperfused between 4 and 8 am (p Conclusion This study suggests that the circadian clock could temporarily affect outcomes after lung transplantation due to recipient-donor circadian desynchrony. Ligands targeting the clock protein REVERBα repress key PGD biomarkers showing that this is a tractable therapeutic pathway." @default.
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- W2768350982 date "2017-11-15" @default.
- W2768350982 modified "2023-09-23" @default.
- W2768350982 title "S16 Circadian control of primary lung allograft dysfunction, mediated by the clock protein, reverbα" @default.
- W2768350982 doi "https://doi.org/10.1136/thoraxjnl-2017-210983.22" @default.
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