Fraser Simon D, Crooks Michael G, Kaye Paul M, Hart Simon P
Respiratory Research Group, Hull York Medical School, Castle Hill Hospital, Cottingham, UK.
York Biomedical Research Institute, Hull York Medical School, University of York, York, UK.
ERJ Open Res. 2021 Mar 15;7(1). doi: 10.1183/23120541.00804-2020. eCollection 2021 Jan.
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.
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.
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 CD200R phenotype and 11 out of 25 (44%) having a CD200R phenotype. These distinct sarcoidosis monocyte phenotypes remained consistent over time.
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.
在结节病中，血液单核细胞作为肉芽肿巨噬细胞的循环前体，表现出炎性细胞因子产生增强、调节（抑制）性受体CD200R表达降低以及由CD14和CD16定义的亚群改变。调节性受体用于抑制单核细胞和巨噬细胞的炎症反应。我们研究了结节病中单核细胞亚群与调节性受体表达之间的关系。
采用多参数流式细胞术对慢性肺结节病患者和年龄匹配的健康对照者新鲜分离的血液免疫细胞表面调节分子进行详细分析。
招募了25例未服用口服糖皮质激素或其他免疫调节剂的慢性肺结节病患者（疾病中位病程22个月）。非经典单核细胞在结节病中增多，与经典或中间单核细胞相比，其调节性受体CD200R、信号调节蛋白-α和CD47的表达显著降低。在结节病中，与健康对照相比，所有三个单核细胞亚群的CD200R和CD47表达均显著降低。在结节病患者群体的经典和中间单核细胞上观察到CD200R的二分分布，25例结节病患者中有14例（56%）具有CD200R⁺表型，25例中有11例（44%）具有CD200R⁻表型。这些不同的结节病单核细胞表型随时间保持一致。
在结节病中增多的非经典单核细胞表达极低水平的调节性受体。经典和中间单核细胞中CD200R表达的两种不同且持久的表型可作为结节病生物标志物进行评估。
