@article{a86d4ae3237e4dd7a99e75af022de279,
title = "Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation",
abstract = "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 1 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.",
keywords = "Acute inflammation, Haematopoiesis, Monocytes and macrophages, Mucosal immunology",
author = "Mirchandani, {Ananda S.} and Jenkins, {Stephen J.} and Bain, {Calum C.} and Sanchez-Garcia, {Manuel A.} and Hannah Lawson and Patricia Coelho and Fiona Murphy and Griffith, {David M.} and Ailiang Zhang and Tyler Morrison and Tony Ly and Simone Arienti and Pranvera Sadiku and Watts, {Emily R.} and Dickinson, {Rebecca S.} and Leila Reyes and George Cooper and Sarah Clark and David Lewis and Van Kelly and Christos Spanos and Musgrave, {Kathryn M.} and Liam Delaney and Isla Harper and Jonathan Scott and Parkinson, {Nicholas J.} and Rostron, {Anthony J.} and Baillie, {J. Kenneth} and Sara Clohisey and Clare Pridans and Lara Campana and Lewis, {Philip Starkey} and Simpson, {A. John} and Dockrell, {David H.} and J{\"u}rgen Schwarze and Nikhil Hirani and Ratcliffe, {Peter J.} and Pugh, {Christopher W.} and Kamil Kranc and Forbes, {Stuart J.} and Whyte, {Moira K.B.} and Walmsley, {Sarah R.}",
note = "Funding Information: This work was funded by a Wellcome Trust Senior Clinical fellowship awarded to S.R.W. (grant nos. 098516 and 209220), Wellcome Trust Post-doctoral Training Clinical Fellowship (grant no. 110086) and a Wellcome Trust iTPA grant (no. PIII052) awarded to A.S.M., and was partly funded by UK Research and Innovation/National Institute for Health and Care Research (NIHR) through the UK Coronavirus Immunology Consortium. C.C.B holds a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant no. 206234/Z/17/Z). K.K.{\textquoteright}s laboratory is supported by grants from Cancer Research UK (nos. C29967A/14633 and C29967/A26787), MRC, the Bart{\textquoteright}s Charity, the Kay Kendall Leukaemia Fund and Blood Cancer UK. A.J.S. is an NIHR Senior Investigator. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = jun,
doi = "10.1038/s41590-022-01216-z",
language = "English",
volume = "23",
pages = "927--939",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Research",
}