Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.1016/j.cbi.2024.111011
Lizenz creative commons licence
Titel (primär) Single and mixture effects of bisphenol A and benzophenone-3 on in vitro T helper cell differentiation
Autor Fischer, F.; Ermer, M.R.; Howanski, J.; Yin, Z.; Bauer, M.; Wagner, M.; Fink, B.; Zenclussen, A.C.; Schumacher, A.
Quelle Chemico-Biological Interactions
Erscheinungsjahr 2024
Department IMMU
Band/Volume 395
Seite von art. 111011
Sprache englisch
Topic T9 Healthy Planet
Keywords TH17 cell; regulatory T cell; in vitro differentiation; endocrine disruptor; bisphenol A; benzophenone-3; chemical mixture

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 (Treg) 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 Treg cell intermediate states. While BPA and BP-3 promoted the development of TH1-like TH17 cells under TH17-differentiating conditions, TH2-like Treg cells occurred under Treg 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.

dauerhafte UFZ-Verlinkung
Fischer, F., Ermer, M.R., Howanski, J., Yin, Z., Bauer, M., Wagner, M., Fink, B., Zenclussen, A.C., Schumacher, A. (2024):
Single and mixture effects of bisphenol A and benzophenone-3 on in vitro T helper cell differentiation
Chem.-Biol. Interact. 395 , art. 111011 10.1016/j.cbi.2024.111011