TY - JOUR T1 - Distinct immune regulatory receptor profiles linked to altered monocyte subsets in sarcoidosis JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00804-2020 SP - 00804-2020 AU - Simon D. Fraser AU - Michael G. Crooks AU - Paul M. Kaye AU - Simon P. Hart Y1 - 2020/01/01 UR - http://openres.ersjournals.com/content/early/2020/12/10/23120541.00804-2020.abstract N2 - Background In sarcoidosis, blood monocytes, circulating precursors of granuloma macrophages, display enhanced inflammatory cytokine production, reduced expression of the regulatory (inhibitory) receptor CD200R, and altered subsets defined by CD14 and CD16. Regulatory receptors serve to dampen monocyte and macrophage inflammatory responses. We investigated the relationship between monocyte subsets and regulatory receptor expression in sarcoidosis.Methods Multi-parameter flow cytometry was used to perform detailed analyses of cell surface regulatory molecules on freshly isolated blood immune cells from patients with chronic pulmonary sarcoidosis and age-matched healthy controls.Results Twenty-five patients with chronic pulmonary sarcoidosis (median duration of disease 22 months) who were not taking oral corticosteroids or other immunomodulators were recruited. Non-classical monocytes were expanded in sarcoidosis and exhibited significantly lower expression of regulatory receptors CD200R, SIRP-α, and CD47 than classical or intermediate monocytes. In sarcoidosis, all three monocyte subsets had significantly reduced CD200R and CD47 expression compared with healthy controls. A dichotomous distribution of CD200R was seen on classical and intermediate monocytes in the sarcoidosis population, with 14/25 (56%) sarcoidosis patients having a CD200R-low phenotype, and 11/25 (44%) CD200R-high. These distinct sarcoidosis monocyte phenotypes remained consistent over time.Conclusion Non-classical monocytes, which are expanded in sarcoidosis, express very low levels of regulatory receptors. Two distinct and persistent phenotypes of CD200R expression in classical and intermediate monocytes could be evaluated as sarcoidosis biomarkers.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Dr. Fraser reports grants from SarcoidosisUK/British Lung Foundation, during the conduct of the study.Conflict of interest: Dr. Crooks reports grants from SarcoidosisUK/British Lung Foundation, during the conduct of the study.Conflict of interest: Dr. Kaye reports grants from SarcoidosisUK/British Lung Foundation, during the conduct of the study.Conflict of interest: Dr. Hart reports grants from SarcoidosisUK/British Lung Foundation, during the conduct of the study. ER -