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

Marie Liamin (1, 2) , Hélène Le Mentec (1, 2) , Bertrand Evrard (1) , Laurence Huc (3) , Frédéric Chalmel (1) , Elisa Boutet-Robinet (3) , E. Le Ferrec (1, 2) , Lydie Sparfel (1, 2)

1 Irset - Institut de recherche en santé, environnement et travail
2 UR Pharmacie - Université de Rennes - Faculté des sciences pharmaceutiques et biologiques
3 ToxAlim-COMICS - Contaminants & Stress Cellulaire

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[]pyrene (B[]P), using a microarray-based transcriptome analysis. After a 48 h exposure to B[]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 (CYP) 1A1 and 1B1, but also others not previously shown to be targeted by B[]P such as genes encoding the gap junction beta (GJB)-2 and 6 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[]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.

Mots clés: immunotoxicity; benzo[α]pyrene; T lymphocytes; microarrays; migration

Domaines: Toxicologie

Marie Liamin, Hélène Le Mentec, Bertrand Evrard, Laurence Huc, Frédéric Chalmel, et al.. Genome-Wide Transcriptional and Functional Analysis of Human T Lymphocytes Treated with Benzo[α]pyrene. International Journal of Molecular Sciences, 2018, 19 (11), pp.E3626. ⟨10.3390/ijms19113626⟩. ⟨hal-01940253⟩