Aryl hydrocarbon receptor (AhR) agonists failed to induce AhR-mediated cytokine gene transcription in bovine PBMCs 2053

Abstract Description The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that senses dioxin-like environmental pollutants, dietary, microbial and cellular metabolites and induces expression of hundreds of genes including xenobiotic metabolizing enzymes CYP1A1 and CYP1B1. Since AhR agonists can modulate immune system, AhR agonists have been recently tested as vaccine adjuvants. Bovine PBMCs subsets that express AhR or respond to AhR agonists is currently unknown. RT-qPCR analyses revealed stimulation of PBMCs with AhR agonists β-naphthoflavone (βNAP) and indole-3-carbinol (I3C), but not 3,3’-diindolylmethane, increased CYP1A1 and CYP1B1 transcript levels. No upregulation of AhR, ARNT, NQO1, FOXP3, IL-17, or IL-22 transcripts were observed. PrimeFlow RNA assay revealed expression of AhR transcripts in all PBMCs subsets. Although mitogen (PMA/IONO) stimulation resulted in increased cytokine transcripts of IFN-γ (Th1 cells), IL-4 (Th2 cells), IL-17 (Th17 cells), and IL-22 (Th22 cells), AhR agonist (β-NAP) failed to induce IFN-γ, IL-4, FOXP3, IL-17 or IL-22 transcripts in respective cell subsets. Interestingly, β-NAP induced CYP1A1 transcript levels only in monocytes. These findings suggest that despite expression of AhR transcripts in all PBMCs subsets, only monocytes responded to AhR agonists (βNAP and I3C) with increased of CYP1A1 and CYP1B1 transcription. Due to the lack of cytokine genes induction, tested AhR agonists may not be suitable as vaccine adjuvant for cattle Funding Sources USDA CRIS 5030-32000-229-000-D Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)