The continuum of monocyte phenotypes: Experimental evidence and prognostic utility in assessing cardiovascular risk

Cignarella, Andrea; Tedesco, Serena; Cappellari, Roberta; Fadini, Gian Paolo

doi:10.1002/jlb.5ru1217-477rr

Cited by 25 publications

(19 citation statements)

References 64 publications

(82 reference statements)

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“…Results from manual analysis of flow cytometric data were further validated by means of an unsupervised clustering algorithm (CITRUS, as implemented in the cloud-based Cytobank software, Cytobank Inc. USA). This approach accounts for the continuous nature of immune subsets (e.g., monocyte subpopulations) and has been shown to better reflect pathophysiologic conditions than gating-based, threshold-driven manual analysis of distinct subtypes ( 23 ). Briefly, CITRUS performs hierarchical clustering of cellular populations based on phenotypical similarity and automatically identifies stratifying features between groups ( 24 ).…”

Section: Methodsmentioning

confidence: 99%

Pro-inflammatory Monocyte Phenotype and Cell-Specific Steroid Signaling Alterations in Unmedicated Patients With Major Depressive Disorder

et al. 2018

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Several lines of evidence have strongly implicated inflammatory processes in the pathobiology of major depressive disorder (MDD). However, the cellular origin of inflammatory signals and their specificity remain unclear. We examined the phenotype and glucocorticoid signaling in key cell populations of the innate immune system (monocytes) vs. adaptive immunity (T cells) in a sample of 35 well-characterized, antidepressant-free patients with MDD and 35 healthy controls individually matched for age, sex, smoking status and body mass index. Monocyte and T cell phenotype was assessed by flow cytometry. Cell-specific steroid signaling was determined by mRNA expression of pre-receptor regulation (11β-hydroxysteroid dehydrogenase type 1; 11β -HSD1), steroid receptor expression [glucocorticoid receptor (GR) and mineralocorticoid receptor (MR)], and the downstream target glucocorticoid-induced leucine-zipper (GILZ). We also collected salivary cortisol samples (8:00 a.m. and 10:00 p.m.) on two consecutive days. Patients showed a shift toward a pro-inflammatory phenotype characterized by higher frequency and higher absolute numbers of non-classical monocytes. No group differences were observed in major T cell subset frequencies and phenotype. Correspondingly, gene expression indicative of steroid resistance (i.e., lower expression of GR and GILZ) in patients with MDD was specific to monocytes and not observed in T cells. Monocyte phenotype and steroid receptor expression was not related to cortisol levels or serum levels of IL-6, IL-1β, or TNF-α. Our results thus suggest that in MDD, cells of the innate and adaptive immune system are differentially affected with shifts in monocyte subsets and lower expression of steroid signaling related genes.

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Section: Methodsmentioning

confidence: 99%

Pro-inflammatory Monocyte Phenotype and Cell-Specific Steroid Signaling Alterations in Unmedicated Patients With Major Depressive Disorder

et al. 2018

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“…1B "nonclassical" CD14 + /lowCD16 + macrophages in the sputum, 31 which have been shown to have distinct functions. 32,33 Monocytes and macrophages from sputum were predominantly CD16 + (nonclassical; Fig. 1C) and were lower in AS patients (AS 12.2% vs. HC 25.8%).…”

Section: Altered Frequency Of Immune Cell Subsets In Asthmatic Patientsmentioning

confidence: 99%

Profiling cellular heterogeneity in asthma with single cell multiparameter CyTOF

Stewart

Wang

Chupp

et al. 2020

Journal of Leukocyte Biology

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Asthma is a chronic inflammatory disease of the airways that afflicts over 30 million individuals in the United States and over 300 million individuals worldwide. The inflammatory response in the airways is often characterized by the analysis of sputum, which contains multiple types of cells including neutrophils, macrophages, lymphocytes, and rare bronchial epithelial cells. Subtyping patients using microscopy of the sputum has identified both neutrophilic and eosinophilic infiltrates in airway inflammation. However, with the extensive heterogeneity among these cell types, a higher resolution understanding of the inflammatory cell types present in the sputum is needed to dissect the heterogeneity of disease. Improved recognition of the distinct phenotypes and sources of inflammation in asthmatic granulocytes may identify relevant pathways for clinical management or investigation of novel therapeutic mediators. Here, we employed mass cytometry or cytometry by time-of-flight to quantify frequency and define functional status of sputum derived airway cells in asthmatic patients and healthy controls. This in-depth single cell analysis method identified multiple distinct subtypes of airway immune cells, especially in neutrophils. Significance was discovered by statistical analysis as well as a data-driven unbiased clustering approach. Our multidimensional assessment method identifies differences in cellular function and supports identification of cellular status that may contribute to diverse clinical responses. This technical advance is relevant for studies of pathogenesis and may provide meaningful insights to advance our knowledge of asthmatic inflammation.

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“…Gating strategy based on CD14 and CD16 is the most popular classification method for the monocyte subsets among studies on coronary atherosclerosis [15]. The expression levels of CD14 and CD16 on monocyte subsets have obvious individual specificity [16]. And CD14 and CD16 expression levels will change with environmental stimuli [17,18].…”

Section: Ivyspring International Publishermentioning

confidence: 99%

Lower HDL-C levels are associated with higher expressions of CD16 on monocyte subsets in coronary atherosclerosis

Xiang¹,

Liang²,

Zhang³

et al. 2020

Int. J. Med. Sci.

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Background: Increased expressions of CD16 on classical monocytes precede their transition to intermediate monocytes. Thus far, the influence of lipids on the expression of CD14 and CD16 on monocyte subsets in coronary atherosclerosis (CA) remains unclear. The aim of this study was to investigate the underlying association between blood lipids and the expression of CD14 and CD16 on monocyte subsets. Methods: This study enrolled 112 healthy controls and 110 CA patients. Monocyte subsets [CD14 ++ CD16-(classical), CD14 ++ CD16 + (intermediate) and CD14 + CD16 ++ (non-classical)] were analyzed by flow cytometry. Median fluorescent intensity (MFI) was used to evaluate the expression levels of CD14 and CD16 on monocyte subsets. Results: Compared with the control group, the expression of CD16 was significantly increased on all three monocyte subsets in the patient group. Correlation analysis revealed that serum HDL-C was inversely associated with the expression of CD16 on intermediate monocytes after Bonferroni correction in the control group. In addition, a significant decrease in classical monocytes and an increase in intermediate monocytes were detected in patients. In linear regression analysis, intermediate monocytes showed an inverse association with serum HDL-C in the control group. Although CD14 was correlated with serum TC and HDL-C, there was no statistical difference in CD14 expression between the two groups. Conclusion: Low serum HDL-C may induce upregulation of CD16 on classical monocytes, which may in turn lead to the increase of intermediate monocytes in coronary atherosclerosis patients.

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The continuum of monocyte phenotypes: Experimental evidence and prognostic utility in assessing cardiovascular risk

Cited by 25 publications

References 64 publications

Pro-inflammatory Monocyte Phenotype and Cell-Specific Steroid Signaling Alterations in Unmedicated Patients With Major Depressive Disorder

Pro-inflammatory Monocyte Phenotype and Cell-Specific Steroid Signaling Alterations in Unmedicated Patients With Major Depressive Disorder

Profiling cellular heterogeneity in asthma with single cell multiparameter CyTOF

Lower HDL-C levels are associated with higher expressions of CD16 on monocyte subsets in coronary atherosclerosis

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