Genome-Wide Transcriptional and Functional Analysis of Human T Lymphocytes Treated with Benzo[<i>α</i>]pyrene

• Main Authors: Marie Liamin, Hélène Le Mentec, Bertrand Evrard, Laurence Huc, Frédéric Chalmel, Elisa Boutet-Robinet, Eric Le Ferrec, Lydie Sparfel
• Format: Article
• Language: English
• Published: MDPI AG 2018-11-01
• Series: International Journal of Molecular Sciences
• Subjects: benzo[<i>α</i>]pyrene; T lymphocytes; microarrays; migration; immunotoxicity
• Online Access: https://www.mdpi.com/1422-0067/19/11/3626

Polycyclic aromatic hydrocarbons (PAHs) are widely distributed environmental contaminants, known to affect T lymphocytes. However, the molecular targets and pathways involved in their immunotoxic effects in human T lymphocytes remain unknown. Here, we analyzed the gene expression profile of primary human T lymphocytes treated with the prototypical PAH, benzo[<i>&#945;</i>]pyrene (B[<i>&#945;</i>]P), using a microarray-based transcriptome analysis. After a 48 h exposure to B[<i>&#945;</i>]P, we identified 158 genes differentially expressed in T lymphocytes, including not only genes well-known to be affected by PAHs such as the cytochromes P450 (<i>CYP</i>) <i>1A1</i> and <i>1B1</i>, but also others not previously shown to be targeted by B[<i>&#945;</i>]P such as genes encoding the gap junction beta (<i>GJB</i>)-<i>2</i> and <i>6</i> proteins. Functional enrichment analysis revealed that these candidates were significantly associated with the aryl hydrocarbon (AhR) and interferon (IFN) signaling pathways; a marked alteration in T lymphocyte recruitment was also observed. Using functional tests in transwell migration experiments, B[<i>&#945;</i>]P was then shown to significantly decrease the chemokine (C-X-C motif) ligand 12-induced chemotaxis and transendothelial migration of T lymphocytes. In total, this study opens the way to unsuspected responsive pathway of interest, i.e., T lymphocyte migration, thus providing a more thorough understanding of the molecular basis of the immunotoxicity of PAHs.