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Persistent immunosuppressive effects of dibutyl phthalate exposure in adult male mice
Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Environmental Science.ORCID iD: 0000-0002-6111-7435
Stockholm University, Faculty of Science, Department of Environmental Science. Stockholm University, Science for Life Laboratory (SciLifeLab).ORCID iD: 0000-0002-1889-196X
Stockholm University, Faculty of Science, Department of Environmental Science. Stockholm University, Science for Life Laboratory (SciLifeLab).ORCID iD: 0000-0001-6140-0209
Stockholm University, Faculty of Science, Department of Environmental Science. Stockholm University, Science for Life Laboratory (SciLifeLab).
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Number of Authors: 52023 (English)In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 878, article id 162741Article in journal (Refereed) Published
Abstract [en]

Increased exposure to manmade chemicals may be linked to an increase in immune-related diseases in humans and immune system dysfunction in wildlife. Phthalates are a group of endocrine-disrupting chemicals (EDCs) suspected to influence the immune system. The aim of this study was to characterize the persistent effects on leukocytes in the blood and spleen, as well as plasma cytokine and growth factor levels, one week after the end of five weeks of oral treatment with dibutyl phthalate (DBP; 10 or 100 mg/kg/d) in adult male mice. Flow cytometry analysis of the blood revealed that DBP exposure decreased the total leukocyte count, classical monocyte and T helper (Th) popula-tions, whereas it increased the non-classical monocyte population compared to the vehicle control (corn oil). Immuno-fluorescence analysis of the spleen showed increased CD11b+Ly6G+ (marker of polymorphonuclear myeloid-derived suppressor cells; PMN-MDSCs), and CD43+staining (marker of non-classical monocytes), whereas CD3+ (marker of total T cells) and CD4+ (marker of Th cells) staining decreased. To investigate the mechanisms of action, levels of plasma cytokines and chemokines were measured using multiplexed immunoassays and other key factors were ana-lyzed using western blotting. The observed increase in M-CSF levels and the activation of STAT3 may promote PMN-MDSC expansion and activity. Increased ARG1, NOX2 (gp91phox), and protein nitrotyrosine levels, as well as GCN2 and phosphor-eIRF alpha, suggest that oxidative stress and lymphocyte arrest drive the lymphocyte suppression caused by PMN-MDSCs. The plasma levels of IL-21 (promotes the differentiation of Th cells) and MCP-1 (regulates mi-gration and infiltration of monocytes/macrophages) also decreased. These findings show that adult DBP exposure can cause persistent immunosuppressive effects, which may increase susceptibility to infections, cancers, and immune dis-eases, and decrease vaccine efficacy.

Place, publisher, year, edition, pages
2023. Vol. 878, article id 162741
Keywords [en]
Cytokines, Endocrine-disrupting chemical, Immunotoxicity, Leukocytes, Oxidative stress, PMN-MDSC
National Category
Immunology
Identifiers
URN: urn:nbn:se:su:diva-216997DOI: 10.1016/j.scitotenv.2023.162741ISI: 000969122500001PubMedID: 36914131Scopus ID: 2-s2.0-85158016128OAI: oai:DiVA.org:su-216997DiVA, id: diva2:1759565
Available from: 2023-05-26 Created: 2023-05-26 Last updated: 2023-05-26Bibliographically approved

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Pierozan, PaulaKällsten, LiselottTheodoropoulou, EleftheriaAlmamoun, RadwaKarlsson, Oskar

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