Single and mixture effects of bisphenol A and benzophenone-3 on in vitro T helper cell differentiation

Florence Fischer; Miriam Rebecca Ermer; Julia Howanski; Ziran Yin; Mario Bauer; Marita Wagner; Beate Fink; Ana C Zenclussen; Anne Schumacher

doi:10.1016/j.cbi.2024.111011

Single and mixture effects of bisphenol A and benzophenone-3 on in vitro T helper cell differentiation

Chem Biol Interact. 2024 Apr 21:395:111011. doi: 10.1016/j.cbi.2024.111011. Online ahead of print.

Authors

Florence Fischer¹, Miriam Rebecca Ermer¹, Julia Howanski¹, Ziran Yin¹, Mario Bauer², Marita Wagner², Beate Fink², Ana C Zenclussen¹, Anne Schumacher³

Affiliations

¹ Department of Environmental Immunology, Helmholtz Centre for Environmental Research GmbH - UFZ, Permoserstraße 15, 04318, Leipzig, Germany; Perinatal Immunology, Saxonian Incubator for Clinical Translation (SIKT), Medical Faculty, Leipzig University, Philipp-Rosenthal-Straße 55, 04103, Leipzig, Germany.
² Department of Environmental Immunology, Helmholtz Centre for Environmental Research GmbH - UFZ, Permoserstraße 15, 04318, Leipzig, Germany.
³ Department of Environmental Immunology, Helmholtz Centre for Environmental Research GmbH - UFZ, Permoserstraße 15, 04318, Leipzig, Germany; Perinatal Immunology, Saxonian Incubator for Clinical Translation (SIKT), Medical Faculty, Leipzig University, Philipp-Rosenthal-Straße 55, 04103, Leipzig, Germany. Electronic address: anne.schumacher@ufz.de.

PMID: 38653352
DOI: 10.1016/j.cbi.2024.111011

Abstract

Immune homeostasis is key to guarantee that the immune system can elicit effector functions against pathogens and at the same time raise tolerance towards other antigens. A disturbance of this delicate balance may underlie or at least trigger pathologies. Endocrine disrupting chemicals (EDCs) are increasingly recognized as risk factors for immune dysregulation. However, the immunotoxic potential of specific EDCs and their mixtures is still poorly understood. Thus, we aimed to investigate the effect of bisphenol A (BPA) and benzophenone-3 (BP-3), alone and in combination, on in vitro differentiation of T helper (TH)17 cells and regulatory T (T_reg) cells. Naïve T cells were isolated from mouse lymphoid tissues and differentiated into the respective TH population in the presence of 0.001-10 μM BP-3 and/or 0.01-100 μM BPA. Cell viability, proliferation and the expression of TH lineage specific transcription factors and cytokines was measured by flow cytometry and CBA/ELISA. Moreover, the transcription of hormone receptors as direct targets of EDCs was quantified by RT-PCR. We found that the highest BPA concentration adversely affected TH cell viability and proliferation. Moreover, the general differentiation potential of both TH populations was not altered in the presence of both EDCs. However, EDC exposure modulated the emergence of TH17 and T_reg cell intermediate states. While BPA and BP-3 promoted the development of TH1-like TH17 cells under TH17-differentiating conditions, TH2-like T_reg cells occurred under T_reg polarization. Interestingly, differential effects could be observed in mixtures of the two tested compounds compared with the individual compounds. Notably, estrogen receptor β expression was decreased under TH17-differentiating conditions in the presence of BPA and BP-3 as mixture. In conclusion, our study provides solid evidence for both, the immune disruptive potential and the existence of cumulative effects of real nature EDC mixtures on T cell in vitro differentiation.

Keywords: Benzophenone-3; Bisphenol A; Chemical mixture; Endocrine disruptor; In vitro differentiation; Regulatory T cell; TH17 cell.