Plasma microparticles from patients with systemic lupus erythematosus modulate the content of miRNAs in U937 cells
Liseth Carmona-Pérez1, Mauricio Rojas1,2, Carlos Muñoz-Vahos3,4
1Grupo de Inmunología Celular e Inmunogenética (GICIG), Facultad de Medicina, Instituto de Investigaciones Médicas, Universidad de Antioquia (UDEA), Medellín, Colombia.
Abstract:
In systemic lupus erythematosus (SLE), the clearance of apoptotic cells and microparticles (MPs) is reduced. Some MPs contain molecules that can modulate immune responses. This study aimed to evaluate the presence of miR-126 and miR-146a in plasma MPs of patients with SLE (SLE MPs) and analyse the ability of MPs to modulate some events in the promonocytic U937 cell line. Circulating MPs were isolated from plasma samples of healthy controls (HCs), patients with SLE and other autoimmune diseases (OAD). MPs were analysed for size and cell origin by flow cytometry and content of miR-126 and miR-146a by RT-qPCR. MPs were then added to U937 cell cultures to evaluate changes in cell phenotype, cytokine expression, content of miR-126 and miR-146a, and levels of IRF5. Patients with active SLE (aSLE) showed an increase in concentration of plasma MPs that positively correlated with the SLEDAI (SLE Disease Activity Index) score. CD14+ MPs were significantly more abundant in patients with SLE than HCs. SLE MPs contained decreased levels of miR-146a, but the miR-126 content in aSLE MPs was increased. The miR-126 content in SLE MPs correlated positively with the SLEDAI score. The treatment of U937 cells with MPs from HCs and patients induced reduced expression of HLA-DR, CD18 and CD119, increased frequency of IL-6+ and TNF-α+ cells, accumulation of IL-8 in culture supernatants, increased miR-126 levels and decreased miR-146a content, but no change in the expression of IRF5. These findings suggest that plasma MPs, especially SLE MPs, could modulate some biological events in U937 cells.
Insights
Systemic lupus erythematosus (SLE) patients have increased microparticles (MPs) containing altered microRNAs (miRNAs). These SLE MPs modulate immune cell responses, suggesting a role in disease pathogenesis.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Reduced clearance of apoptotic cells and microparticles (MPs) is characteristic of systemic lupus erythematosus (SLE).
- MPs can carry immune-modulating molecules, influencing disease processes.
- Specific microRNAs (miRNAs), miR-126 and miR-146a, are implicated in immune regulation.
Purpose of the Study:
- To investigate the presence and levels of miR-126 and miR-146a within plasma MPs from SLE patients.
- To analyze the functional capacity of SLE-derived MPs in modulating immune cell responses using the U937 cell line.
Main Methods:
- Isolation and characterization of circulating MPs from plasma of healthy controls (HCs), SLE patients, and patients with other autoimmune diseases (OAD) using flow cytometry.
- Quantification of miR-126 and miR-146a content in MPs via RT-qPCR.
- Incubation of U937 cells with isolated MPs to assess changes in cell phenotype, cytokine expression, miRNA levels, and IRF5 expression.
Main Results:
- Active SLE patients exhibited higher plasma MP concentrations, correlating with SLE Disease Activity Index (SLEDAI) scores.
- CD14+ MPs were significantly more abundant in SLE patients compared to HCs.
- SLE MPs showed decreased miR-146a and increased miR-126 levels, with miR-126 positively correlating with SLEDAI.
- MP treatment of U937 cells altered immune marker expression (HLA-DR, CD18, CD119), increased pro-inflammatory cytokines (IL-6, TNF-α, IL-8), and modified intracellular miRNA levels, but not IRF5.
Conclusions:
- Plasma MPs, particularly those from SLE patients, are altered in miRNA content and can modulate immune cell behavior.
- These findings highlight a potential role for SLE-derived MPs and their miRNA cargo in the immune dysregulation observed in SLE.
- Further research into SLE MPs could reveal novel diagnostic or therapeutic targets.
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