Benzo[a]pyrene exposure causes exonal switch resulting in reduced surface CD5 expression in an AHR-dependent manner

Area of Science:

• Immunology
• Molecular Biology
• Environmental Health

Background:

• CD5 protein's surface expression in T cells is crucial but not fully understood.
• Variations in CD5 surface expression link to immunopathology and hematological malignancies.
• An alternative exon (E1B) from human endogenous retroviruses (HERV) downregulates conventional CD5 (E1A) expression, leading to intracellular retention (cCD5).

Purpose of the Study:

• Investigate the regulation of CD5 alternative exon (E1B) expression.
• Determine the role of dioxin exposure and the aryl hydrocarbon receptor (AHR) in CD5 regulation.
• Understand the impact of polycyclic aromatic hydrocarbons on T cell function via CD5 modulation.

Main Methods:

• In silico transcription factor binding site (TFBS) analysis of the E1B upstream region.
• Exposure of cells to benzo[a]pyrene (BaP) and analysis of E1A/E1B expression.
• Chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) to confirm AHR binding.
• AHR inhibition and gene silencing studies.

Main Results:

• Five putative Dioxin Response Elements (DREs) were identified in the E1B upstream region.
• BaP exposure upregulated E1B expression while downregulating E1A expression and both surface (sCD5) and intracellular (cCD5) proteins.
• ChIP-qPCR confirmed AHR binding to predicted DRE sites.
• AHR involvement in the exonal switch was confirmed through inhibitor and gene silencing experiments.

Conclusions:

• Polycyclic aromatic hydrocarbons decrease sCD5 expression by upregulating alternative exon E1B expression via AHR.
• This mechanism, involving an AHR-mediated exonal switch, may negatively impact T cell functions.
• The findings highlight a novel pathway linking environmental pollutants to altered immune cell function.