Reduced expression of monocyte CD200R is associated with enhanced proinflammatory cytokine production in sarcoidosis

Fraser, Simon D.; Sadofsky, Laura R.; Kaye, Paul M.; Hart, Simon P.

Abstract

In sarcoidosis, the proinflammatory cytokines interferon gamma, tumour necrosis factor and interleukin-6 are released by monocyte-derived macrophages and lymphocytes in the lungs and other affected tissues. Regulatory receptors expressed on monocytes and macrophages act to suppress cytokine production, and reduced expression of regulatory receptors may thus promote tissue inflammation. The aim of this study was to characterise the role of regulatory receptors on blood monocytes in patients with sarcoidosis. Cytokine release in response to stimulation of whole blood was measured in healthy controls and Caucasian non-smoking patients with sarcoidosis who were not taking disease modifying therapy. Expression of the regulatory molecules IL-10R, SIRP-α/β, CD47, CD200R, and CD200L was measured by flow cytometry, and functional activity was assessed using blocking antibodies. Stimulated whole blood and monocytes from patients with sarcoidosis produced more TNF and IL-6 compared with healthy controls. 52.9% of sarcoidosis patients had monocytes characterised by low expression of CD200R, compared with 11.7% of controls (p < 0.0001). Patients with low monocyte CD200R expression produced higher levels of proinflammatory cytokines. In functional studies, blocking the CD200 axis increased production of TNF and IL-6. Reduced expression of CD200R on monocytes may be a mechanism contributing to monocyte and macrophage hyperactivation in sarcoidosis.

Citation

Fraser, S. D., Sadofsky, L. R., Kaye, P. M., & Hart, S. P. (2016). Reduced expression of monocyte CD200R is associated with enhanced proinflammatory cytokine production in sarcoidosis. Scientific reports, 6(1), Article ARTN 38689. https://doi.org/10.1038/srep38689

• Journal Article Type: Article
• Acceptance Date: Nov 11, 2016
• Online Publication Date: Dec 8, 2016
• Publication Date: Dec 8, 2016
• Deposit Date: Dec 13, 2016
• Publicly Available Date: Dec 13, 2016
• Journal: Scientific reports
• Print ISSN: 2045-2322
• Electronic ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 1
• Article Number: ARTN 38689
• DOI: https://doi.org/10.1038/srep38689
• Keywords: Monocytes and macrophages, Respiratory tract diseases, Translational research
• Public URL: https://hull-repository.worktribe.com/output/472181
• Publisher URL: http://www.nature.com/articles/srep38689
• Additional Information: Copy of: Fraser, S. D. et al. Reduced expression of monocyte CD200R is associated with enhanced proinflammatory cytokine production in sarcoidosis. Sci. Rep. 6, 38689; doi: 10.1038/srep38689 (2016).