Békés Márta1, Petchner Péter2, Fekete Nóra1, Pállinger Éva1, Pálóczi Krisztina1, Buzás Edit1, Tamási Viola1
1 Department of Genetics, Cell- and Immunobiology, Semmelweis University Budapest
2 Department of Pharmacodynamics, Semmelweis University Budapest
Introduction: Living organisms have developed a strategy to protect themselves from xenobiotics. The major players in this strategy are nuclear receptors called xenosensors, which activate xenobiotic metabolism in various cells. Immune cells are also informed about xenobiotic exposure by their xenosensors. Immune response to xenobiotics has been shown in autoimmune processes. Activation of xenosensors also results in inductions of either pro- or anti-inflammatory processes. Many xenobiotics (e.g. drugs) have been shown to influence immune responses, but little attention has been paid whether food additives (e.g. tBHQ terc-butylhydroquinone, E319) have the same effect.
Aims: In our work, we investigated how tBHQ modulates immune response (concretely T-cell differentiation), and what is the role of xenosensors such as NRF2 (Nuclear factor-erythroid2–related factor2) or AHR (Aryl hydrocarbon receptor) in this effect.
Methods: BALB/c mice were fed by tBHQ (2,5 weeks, 1% in diet), and sacrificed. Heterogenous splenocytes, or splenic CD4+ cells were separated with magnetic separation. RNA was isolated for transcriptomic studies (microarray, RT-PCR). Also, in vitro experiments were carried out to investigate the effect of tBHQ on CD4+ T-cell differentiation and to find out which xenosensor mediates this effect.
Results: Our microarray data show that 269 genes changed significantly after per os treatment by tBHQ in CD4+ cells. RT-PCR data proved that the expression of Ahr and Nrf2, and their specific target genes (Cyp1a1, Nqo1) were increased in splenic CD4+ cells. Levels of T-cell differentiation factors (Foxp3, Rorγt,) were significantly increased. Our in vitro studies showed that tBHQ enhanced the differentiation of Th17 cells through NRF2 and AHR.
Conclusions: Our results show that tBHQ changes the expression of many genes in splenic CD4+ cells and modulates the immune response through activation of Th17 cells via the xenosensors AHR and NRF2.
Supported by the Hungarian Scientific Research Found (OTKA-PD 108297, 11958, 120237). NVKP_16-1-2016-0017, János Bolyai Research Scholarship, VEKOP-2.3.3-15-2017-00016.
Doctoral School: Molecular Medicine
Program: Basis of Human Molecular Genetics and Gene Diagnostics
Supervisor: Viola Tamási
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