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Exploring the immunomodulatory effects of environmental contaminants on autoimmune patients: An in vitro approach

Year: 2025
Type: article
Abstract: Background: effects of particulate matter (PM), silica, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on peripheral blood mononuclear cells (PBMCs) from healthy donors (HD) and patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Methods: PBMCs were obtained from HD (n = 6), RA patients (n = 5), and SLE patients (n = 5) and stimulated for 24 h with PM (100 μg/mL), silica (30 μg/mL), or TCDD (250 pg/mL). Immunophenotyping by flow cytometry was performed in HD, characterizing T cell subsets, B cells, NK/NKT cells, monocytes, and dendritic cells, including activation markers. Production of 18 cytokines and chemokines was quantified in all groups using Cytometric Bead Array. Activation of intracellular signaling pathways (AKT, NFκB, p38 MAPK, STAT1, STAT3) was assessed by Western blot. Results: All contaminants induced strong immune activation. In HD, flow cytometry revealed strong activation of monocytes and dendritic cells, with increased co-stimulatory markers (CD40, CD80, CD83) and skewing of T cells toward effector phenotypes. Cytokine analysis showed substantial overlap in inflammatory profiles across HD, RA, and SLE, despite the significant upregulation of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), growth factors (GM-CSF, G-CSF), and regulatory cytokines (IL-10). Western blot confirmed modulation of signaling pathways, with PM notably enhancing p38 MAPK phosphorylation in HD and RA. Conclusion: Environmental contaminants elicit robust immunomodulatory effects in PBMCs. The overlap in cytokine profiles and signaling responses across HD, RA, and SLE indicates a highly conserved cellular response to environmental stressors, independent of autoimmune disease status.
Authors: Yeny Acosta-Ampudia, Diana M. Monsalve, Daniel Galeano-Sánchez, Manuel Rojas, Carolina Ramírez-Santana
Language: English
Subfield: Immunology
Open Access status: gold
Estimated APC paid: $3,180
OpenAlex ID: W7111103610
FWCI: 0.883
Cites: 52
Cited by: 3
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