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

Fraser, Simon D.; Crooks, Michael G.; Kaye, Paul M.; Hart, Simon P.

Authors

Simon D. Fraser

Michael G. Crooks

Paul M. Kaye



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: 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.

Citation

Fraser, S. D., Crooks, M. G., Kaye, P. M., & Hart, S. P. (in press). Distinct immune regulatory receptor profiles linked to altered monocyte subsets in sarcoidosis. ERJ Open Research, https://doi.org/10.1183/23120541.00804-2020

Journal Article Type Article
Acceptance Date Dec 4, 2020
Online Publication Date Dec 17, 2020
Deposit Date Dec 27, 2020
Publicly Available Date Jan 4, 2021
Journal ERJ Open Research
Publisher European Respiratory Society
Peer Reviewed Peer Reviewed
DOI https://doi.org/10.1183/23120541.00804-2020
Public URL https://hull-repository.worktribe.com/output/3682357
Publisher URL https://openres.ersjournals.com/content/early/2020/12/10/23120541.00804-2020

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