title: Reduced expression of monocyte CD200R is associated with enhanced proinflammatory cytokine production in sarcoidosis.
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 hyper-activation in sarcoidosis.
authors.affiliation: Department of Academic Respiratory Medicine, Centre for Cardiovascular and Metabolic Research, Hull York Medical School, Castle Hill Hospital, Cottingham, HU16 5JQ, UK.
authors.forename: Simon D
authors.initials: SD
authors.lastname: Fraser
authors.affiliation: Department of Academic Respiratory Medicine, Centre for Cardiovascular and Metabolic Research, Hull York Medical School, Castle Hill Hospital, Cottingham, HU16 5JQ, UK.
authors.forename: Laura R
authors.initials: LR
authors.lastname: Sadofsky
authors.affiliation: Centre for Immunology and Infection, Department of Biology and Hull York Medical School, University of York, Wentworth Way, York, YO10 5DD, UK.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Kaye
authors.affiliation: Department of Academic Respiratory Medicine, Centre for Cardiovascular and Metabolic Research, Hull York Medical School, Castle Hill Hospital, Cottingham, HU16 5JQ, UK.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Hart
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D000954:Antigens, Surface / Q000235:genetics*; D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism*; D007958:Leukocyte Count; D008231:Lymphopenia; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D064446:Orexin Receptors; D010641:Phenotype; D011485:Protein Binding; D013902:Radiography, Thoracic; D011956:Receptors, Cell Surface / Q000235:genetics*; D012507:Sarcoidosis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D015415:Biomarkers; C477337:CD200R1 protein, human; D016207:Cytokines; D018836:Inflammation Mediators; D064446:Orexin Receptors; D011956:Receptors, Cell Surface; C042739:antigens, CD200