Distinct immune regulatory receptor profiles linked to altered monocyte subsets in sarcoidosis

Abstract

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: Multiparameter 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: 25 patients with chronic pulmonary sarcoidosis (median duration of disease 22 months) who were not taking oral corticosteroids or other immunomodulators were recruited. Nonclassical monocytes were expanded in sarcoidosis and exhibited significantly lower expression of regulatory receptors CD200R, signal regulatory protein-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 out of 25 (56%) sarcoidosis patients having a CD200Rlow phenotype and 11 out of 25 (44%) having a CD200Rhigh phenotype. These distinct sarcoidosis monocyte phenotypes remained consistent over time. Conclusions: Nonclassical 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.