Reduced expression of monocyte CD200R is associated with enhanced proinflammatory cytokine production in sarcoidosis

Fraser, Simon D.; Sadofsky, Laura R.; Kaye, Paul M.; Hart, Simon P.

doi:10.1038/srep38689

Cited by 23 publications

(21 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many studies on sarcoidosis immunology focus on T cells, whereas we here aimed at further investigating sources of innate cytokines. Monocytes are potent cytokine producers 13 , and likely play a role in sarcoidosis [10][11][12] , and we focused our investigations on monocytes in parallel with whole PBMCs. During inflammation, monocytes are recruited to the affected tissue where they can contribute to inflammation both by differentiating to inflammatory DCs and macrophages 22 , but also by producing cytokines including TNF and IL-1β 23 .…”

Section: Discussionmentioning

confidence: 99%

“…Peripheral blood monocytes in sarcoidosis patients display a skewing towards intermediate (CD14 + CD16 + ) monocytes, which are associated with inflammatory conditions 10 – 12 . Further, sarcoidosis monocytes have been found to have a decrease in expression of CD200R, a phenotype associated with inflammatory disease 11 . Moreover, during inflammation in general, monocytes are recruited from peripheral blood to affected tissues and modulate inflammatory processes, in part by releasing large amounts of cytokines 13 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sarcoidosis exosomes stimulate monocytes to produce pro-inflammatory cytokines and CCL2

Wahlund

Akpinar

Steiner

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Pulmonary sarcoidosis has unknown etiology, a difficult diagnostic procedure and no curative treatment. Extracellular vesicles including exosomes are nano-sized entities released from all cell types. Previous studies of exosomes from bronchoalveolar lavage fluid (BALF) of sarcoidosis patients have revealed pro-inflammatory components and abilities, but cell sources and mechanisms have not been identified. In the current study, we found that BALF exosomes from sarcoidosis patients, but not from healthy individuals, induced a dose-dependent elevation of intracellular IL-1β in monocytes. Analyses of supernatants showed that patient exosomes also induced release of IL-1β, IL-6 and TNF from both PBMCs and enriched monocytes, suggesting that the observed effect is direct on monocytes. The potently chemotactic chemokine CCL2 was induced by exosomes from a subgroup of patients, and in a blocking assay the exosome-induced CCL2 was reduced for 13 out of 19 patients by the asthma drug Montelukast, a cysteinyl leukotriene receptor antagonist. Further, reactive oxygen species generation by PBMCs was induced to a higher degree by patient exosomes compared to healthy exosomes. These findings add to an emerging picture of exosomes as mediators and disseminators of inflammation, and open for further investigations of the link between CCL2 and exosomal leukotrienes in sarcoidosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sarcoidosis exosomes stimulate monocytes to produce pro-inflammatory cytokines and CCL2

Wahlund

Akpinar

Steiner

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…For instance, the association between the CD200R expression and inflammatory conditions was reported by Gao et al who noted a negative correlation between CD200R expression on macrophages and C-reactive protein (CRP) levels in patients with rheumatoid arthritis [ 27 ]. Similarly, patients with sarcoidosis and decreased CD200R expression on monocytes had upregulated production of inflammatory cytokines [ 28 ]. However, the same inflammatory cytokines present at the inflammation site trigger CD200 expression, which attenuates the inflammatory response [ 16 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

High CD200 Expression on T CD4+ and T CD8+ Lymphocytes as a Non-Invasive Marker of Idiopathic Pulmonary Hypertension–Preliminary Study

Tomaszewski

Grywalska

Topyła-Putowska

et al. 2021

JCM

View full text Add to dashboard Cite

Pulmonary arterial hypertension (PAH) can develop subsequently to disorganized endothelial cell proliferation within the pulmonary arteriolar layers that provide mechanical limits to the pulmonary vascular bed. Although the actual factor triggering vascular endothelial proliferation remains unknown to date, genetic susceptibility, hypoxia, inflammation, as well as response to drugs and toxins have been proposed as possible contributors. Since inflammation contributes to vascular remodeling, the changed immune response is increasingly considered a plausible cause of this cardiovascular disease. The interaction of a membrane glycoprotein cluster of differentiation 200 (CD200) and its structurally similar receptor (CD200R) plays a crucial role in the modulation of the inflammatory response. Our previous studies have shown that the overexpression of the other negative co-stimulatory molecule (programmed death cell - PD-1) and its ligand-1 (PD-L1) is closely related to iPAH and the presence of Epstein-Barr virus (EBV) reactivation markers. Therefore, we considered it necessary to analyze the different types of PAH in terms of CD200 and CD200R expression and to correlate CD200/CD200R pathway expression with important clinical and laboratory parameters. The CD200/C200R-signaling pathway has not been subject to much research. We included 70 treatment-naïve, newly diagnosed patients with PAH in our study. They were further divided into subsets according to the pulmonary hypertension classification: chronic thromboembolic pulmonary hypertension (CTEPH) subset, pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH), pulmonary arterial hypertension associated with connective tissue disease (CTD-PAH), and idiopathic pulmonary arterial hypertension (iPAH). The control group consisted of 20 healthy volunteers matched for sex and age. The highest percentages of T CD200+CD4+ and T CD200+CD8+ lymphocytes were observed in the group of patients with iPAH and this finding was associated with the presence of EBV DNA in the peripheral blood. Our assessment of the peripheral blood lymphocytes expression of CD200 and CD200R indicates that these molecules act as negative co-stimulators in the induction and persistence of PAH-associated inflammation, especially that of iPAH. Similar results imply that the dysregulation of the CD200/CD200R axis may be involved in the pathogenesis of several immune diseases. Our work suggests that CD200 and CD200R expression may serve to distinguish between PAH cases. Thus, CD200 and CD200R might be useful as markers in managing PAH and should be further investigated.

show abstract

“…Understanding the cellular and molecular drivers of persistent and progressive sarcoidosis will be an important step towards identifying new targets for treatment. Chronic, nonresolving sarcoidosis is characterised immunologically by heightened inflammatory responses of tissue granuloma macrophages and their precursors, circulating blood monocytes (2,5,(10)(11)(12)(13)(14). Cell surface regulatory receptors such as CD200R serve to dampen inflammatory responses in monocytes and macrophages, including reducing production of TNF which is a key cytokine driving granuloma formation and persistence (15,16).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

BackgroundIn 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.MethodsMulti-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.ResultsTwenty-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.ConclusionNon-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.

show abstract

Reduced expression of monocyte CD200R is associated with enhanced proinflammatory cytokine production in sarcoidosis

Cited by 23 publications

References 41 publications

Sarcoidosis exosomes stimulate monocytes to produce pro-inflammatory cytokines and CCL2

Sarcoidosis exosomes stimulate monocytes to produce pro-inflammatory cytokines and CCL2

High CD200 Expression on T CD4+ and T CD8+ Lymphocytes as a Non-Invasive Marker of Idiopathic Pulmonary Hypertension–Preliminary Study

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

Contact Info

Product

Resources

About