Burnham Institute
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http://www.nature.com/ni/journal/v9/n9/abs/ni.1637.html
Article abstract
Nature Immunology 9, 1074 - 1083 (2008)
Published online: 27 July 2008 | doi:10.1038/ni.1637
A critical function for CD200 in lung immune homeostasis and the severity of influenza infection
Robert J Snelgrove1, John Goulding1, Arnaud M Didierlaurent1, Daphne Lyonga1, Seema Vekaria1, Lorna Edwards1, Emily Gwyer1, Jonathon D Sedgwick2, A Neil Barclay3 & Tracy Hussell1
Abstract
The lung must maintain a high threshold of immune 'ignorance' to innocuous antigens to avoid inflammatory disease that depends on the balance of positive inflammatory signals and repressor pathways. We demonstrate here that airway macrophages had higher expression of the negative regulator CD200 receptor (CD200R) than did their systemic counterparts. Lung macrophages were restrained by CD200 expressed on airway epithelium. Mice lacking CD200 had more macrophage activity and enhanced sensitivity to influenza infection, which led to delayed resolution of inflammation and, ultimately, death. The administration of agonists that bind CD200R, however, prevented inflammatory lung disease. Thus, CD200R is critical for lung macrophage immune homeostasis in the resting state and limits inflammatory amplitude and duration during pulmonary influenza infection.
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1. Imperial College London, Kennedy Institute, London, W6 8LH, UK.
2. Eli Lilly, Indianapolis 46285, USA.
3. Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
Article abstract
Nature Immunology 9, 1074 - 1083 (2008)
Published online: 27 July 2008 | doi:10.1038/ni.1637
A critical function for CD200 in lung immune homeostasis and the severity of influenza infection
Robert J Snelgrove1, John Goulding1, Arnaud M Didierlaurent1, Daphne Lyonga1, Seema Vekaria1, Lorna Edwards1, Emily Gwyer1, Jonathon D Sedgwick2, A Neil Barclay3 & Tracy Hussell1
Abstract
The lung must maintain a high threshold of immune 'ignorance' to innocuous antigens to avoid inflammatory disease that depends on the balance of positive inflammatory signals and repressor pathways. We demonstrate here that airway macrophages had higher expression of the negative regulator CD200 receptor (CD200R) than did their systemic counterparts. Lung macrophages were restrained by CD200 expressed on airway epithelium. Mice lacking CD200 had more macrophage activity and enhanced sensitivity to influenza infection, which led to delayed resolution of inflammation and, ultimately, death. The administration of agonists that bind CD200R, however, prevented inflammatory lung disease. Thus, CD200R is critical for lung macrophage immune homeostasis in the resting state and limits inflammatory amplitude and duration during pulmonary influenza infection.
Top of page
1. Imperial College London, Kennedy Institute, London, W6 8LH, UK.
2. Eli Lilly, Indianapolis 46285, USA.
3. Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.