Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation


Nature Immunology

Contributing to research themes:

Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.

Author list:


  1. University of Edinburgh Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
  2. Barts Cancer Research Institute, Queen Mary University of London, London, United Kingdom
  3. Intensive Care Unit, Royal Infirmary of Edinburgh, NHS Lothian
  4. Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh
  5. Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
  6. Department of Respiratory Medicine, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
  7. Roslin Institute, University of Edinburgh, Edinburgh, UK
  8. Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
  9. Nuffield Department of Medicine Research Building, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
  10. Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
  11. The Francis Crick Institute, London, United Kingdom


Ananda S. Mirchandani1*, Stephen J. Jenkins1†, Calum C.Bain1†, Hannah Lawson2, Patricia Coelho1, Fiona Murphy1, David Griffith1, Ailiang Zhang1, Manuel A. Sanchez-Garcia1, Leila Reyes1, Tyler Morrison1, Simone Arienti1, Pranvera Sadiku1, Emily R. Watts1, Rebecca. S. Dickinson1, Sarah Clark3, Tony Ly4, David Lewis4, Van Kelly4, Christos Spanos4, Kathryn M. Musgrave5,6, Liam Delaney1, Isla Harper1, Jonathan Scott5, Nicholas J. Parkinson7, Anthony J. Rostron5, Kenneth J Baillie7,3, Sara Clohisey7, Clare Pridans1, Lara Campana8, Philip Starkey-Lewis8, A John Simpson5, David Dockrell1, 10, Jurgen Schwarze1, Nikhil Hirani1, Peter J. Ratcliffe9,10,11, Christopher W. Pugh9, Kamil Kranc2, Stuart J. Forbes1,8, Moira K. Whyte1, Sarah R. Walmsley1.