Abstract
Atmospheric particulate matter (PM) is a complex component of air pollution that is a composed of inorganic and organic constituents. The chemically-extracted organic fraction (OF) of PM excludes inorganics but retains most organic constituents like polycyclic aromatic hydrocarbons (PAHs). PAHs are ubiquitous environmental toxicants and known aryl hydrocarbon receptor (AHR) ligands. The AHR is a ligand activated transcription factor that responds to endogenous ligands and exogenous ligands including PAHs. Activation of the AHR leads to upregulation of cytochrome P450 (CYP) metabolizing enzymes which are important for the biotransformation of toxicants to less toxic, or in the case of PAHs, more toxic intermediates. Additionally, the AHR plays an important role in balancing regulatory and effector T cell responses. This study aimed to determine whether PAHs present in PM aggravate inflammation by driving inflammatory T cell and dendritic cell (DC) responses and their mechanism of action. This study tests the hypothesis that PAHs present in PM activate the AHR and alter the immune balance shifting from regulation to inflammation. To test this, the effects of SRM1649b OF on T cell differentiation and DC function were measured in vitro. SRM1649b OF enhanced Th17 differentiation in an AHR and CYP-dependent manner and increased the percent of IFNγ positive DCs in an AHR-dependent manner. SRM1649b PAH mixtures enhanced Th17 differentiation in an AHR-dependent but CYP-independent manner and increased the percent of IFNγ positive DCs. Cumulatively, these results suggest that PAHs present in PM are active components that contribute to immune responses in both T cells and BMDCs through the AHR and CYP metabolism. Understanding the role of AHR and CYP metabolism of PAHs in immune cells after PM exposure will shed light on new targets that will shift the immune balance from inflammation to regulation.
Highlights
In recent years, air pollution has emerged as the leading cause of death and disease worldwide and when considering all human pathology related to the environment, air pollution is the primary offender [1]
Our lab demonstrated that an intact standard ambient urban dust particle, SRM1649b particulate matter (PM), increased IL-17 and CYP1A1 mRNA in vivo and enhanced Th17 differentiation in an aryl hydrocarbon receptor (AHR)-dependent manner measured by increased IL-17 mRNA and CYP1A1 mRNA as well as percent IL-17 positive cells in wild-type but not Ahr null cells in vitro [19]
We hypothesized that polycyclic aromatic hydrocarbons (PAHs) present in SRM1649b enhanced Th17 differentiation via the AHR leading to an effector T cell response
Summary
Air pollution has emerged as the leading cause of death and disease worldwide and when considering all human pathology related to the environment, air pollution is the primary offender [1]. Atmospheric particulate matter (PM) is a component of air pollution, and is the largest environmental risk factor for premature death worldwide [1]. The composition of PM varies over time and by location [2] Despite this complexity and variability, all atmospheric PM is currently regulated by total mass based on the assumption that all PM is toxic [3, 4]. This regulatory strategy assumes all PM of the same mass will elicit the same biological effects and ignores individual characteristics and components [3, 4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
