Activated Circulating Myeloid-Derived Suppressor Cells in Patients with Dilated Cardiomyopathy
Insights
Myeloid-derived suppressor cells (MDSCs) are elevated in dilated cardiomyopathy (DCM) patients and suppress T cell function, impacting cardiac health. These findings suggest MDSCs play a role in DCM pathogenesis.
Area of Science:
- Immunology
- Cardiology
- Cell Biology
Background:
- Myeloid-derived suppressor cells (MDSCs) are implicated in inflammatory and autoimmune diseases.
- Elevated MDSC levels are observed in various pathological conditions.
Purpose of the Study:
- To investigate the role and significance of MDSCs in patients with dilated cardiomyopathy (DCM).
- To evaluate the functional characteristics of MDSCs in the context of DCM.
Main Methods:
- Flow cytometry was used to quantify circulating CD14+HLA-DR-/low MDSCs in 42 DCM patients and 39 healthy controls.
- Co-culture models assessed MDSC-mediated suppression of T cell proliferation and interferon-gamma (IFN-γ) production.
- Real-time polymerase chain reaction measured mRNA expression levels of key molecules.
Main Results:
- DCM patients exhibited significantly higher frequencies of circulating CD14+HLA-DR-/low MDSCs compared to healthy controls.
- MDSCs from DCM patients demonstrated enhanced suppression of T cell proliferation and IFN-γ production, partly via arginase-1 (Arg-1).
- MDSC frequencies negatively correlated with left ventricular ejection fraction (LVEF) and positively with N-terminal pro-brain natriuretic peptide (NT-proBNP).
Conclusions:
- Circulating activated MDSCs appear to play a crucial immunomodulatory role in the pathogenesis of DCM.
- MDSC levels and function may serve as potential biomarkers for DCM severity and progression.
Background/Aims:
Myeloid-derived suppressor cells (MDSCs) are increased in inflammatory and autoimmune disorders. This study aims to evaluate the significance of MDSCs in dilated cardiomyopathy (DCM) patients.
Methods:
In total, 42 newly hospitalized DCM patients and 39 healthy controls were enrolled in the study. The frequencies of circulating CD14+HLA-DR-/low MDSCs were determined by flow cytometry. Then, the functional properties of MDSCs in suppressing T cell proliferation and interferon-gamma (IFN-x03B3;) production were measured in a co-culture model. Then, mRNA expression levels of various important molecules in peripheral blood mononuclear cells were measured by real time polymerase chain reaction. Furthermore, correlation analyses between MDSC frequencies and cardiac function parameters were also performed.
Results:
The frequencies of circulating CD14+HLA-DR-/low MDSCs were significantly elevated in DCM patients compared with healthy controls. It showed that MDSCs from DCM patients more effectively suppressed T cell proliferation and IFN-x03B3; production compared with those from healthy controls, which was partially mediated by arginase-1 (Arg-1). In addition, the correlation analysis suggested that MDSC frequencies were negatively correlated with left ventricular ejection fraction (LVEF), while positively with N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with DCM.
Conclusions:
Circulating activated MDSCs might play significant immunomodulatory roles in the pathogenesis of DCM.
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