Environmental exposures alter T cell differentiation and aggravate airway disease through the Aryl Hydrocarbon Receptor (125.6)

Abstract

Abstract Environmental exposures can aggravate airway disease. 10% of World Trade Center disaster responders developed asthma. Polycyclic aromatic hydrocarbon (PAH) levels were the highest ever reported. The Aryl Hydrocarbon Receptor (AHR) directs T-cell differentiation between FoxP3+ Regulatory T-cells and Th17 effector cells, and is the primary receptor for PAHs. Exposure to specific inhaled PAHs found in diesel exhaust particles (DEP), urban dust particles (UDP), and coal fly ash (CFA) has a direct effect on T-cell differentiation in an AHR-dependent manner, that enhances Th17 differentiation and hastens the development of asthma. Naïve CD4+ CD25- T cells from C57BL/6 mice were cultured under Th17 conditions. We utilized standard reference materials (SRM) representing PAHs from UDP, DEP, CFA in cultures and mixed lymphocyte cultures. Human epithelial cells were treated, and then examined for Epithelial to Mesenchymal Transition (EMT), in the presence of PBMC and SRMs. Finally we exposed lungs of mice in vivo to UDP intratracheally (IT). SRMs increased IL-2, IL-17, and IL-22 in the supernatant of naïve T-cells by bead array. SRMs increased IL-17 expression in MLCs. Both IL-17 and UDP were able to cause significant EMT. In lungs exposed to UDP, the AHR was activated and IL-17 was upregulated in tissue by qPCR. PAHs lead to a TH17 deviation in the lung through the AHR. This may play a role in aggravating airway disease in susceptible people, and will be a target for future treatment.