Differential effects of diesel exhaust particles on T cell differentiation and autoimmune disease

Abstract

BackgroundExposure to particulate matter (PM) has been associated with increased incidence and severity of autoimmune disease. Diesel PM is primarily composed of an elemental carbon core and adsorbed organic compounds such as polycyclic aromatic hydrocarbons (PAHs) and contributes up to 40% of atmospheric PM. The organic fraction (OF) of PM excludes all metals and inorganics and retains most organic compounds, such as PAHs. Both PM and OF increase inflammation in vitro and aggravate autoimmune disease in humans. PAHs are known aryl hydrocarbon receptor (AHR) ligands. The AHR modulates T cell differentiation and effector function in vitro and in experimental autoimmune encephalomyelitis (EAE), a murine model of autoimmune disease. This study aims to identify whether the total mass or active components of PM are responsible for activating pathways associated with exposure to PM and autoimmune disease. This study tests the hypothesis that active components present in diesel PM and their OF enhance effector T cell differentiation and aggravate autoimmune disease.ResultsTwo different diesel samples, each characterized for their components, were tested for their effects on autoimmunity. Both diesel PM enhanced effector T cell differentiation in an AHR-dose-dependent manner and suppressed regulatory T cell differentiation in vitro. Both diesel PM aggravated EAE in vivo. Fractionated diesel OFs exhibited the same effects as PM in vitro, but unlike PM, only one diesel OF aggravated EAE. Additionally, both synthetic PAH mixtures that represent specific PAHs found in the two diesel PM samples enhanced Th17 differentiation, however one lost this effect after metabolism and only one required the AHR.ConclusionsThese findings suggest that active components of PM and not total mass are driving T cell responses in vitro, but in vivo the PM matrix and complex mixtures adsorbed to the particles, not just the OF, are contributing to the observed EAE effects. This implies that examining OF alone may not be sufficient in vivo. These data further suggest that bioavailability and metabolism of organics, especially PAHs, may have an important role in vivo.Electronic supplementary materialThe online version of this article (10.1186/s12989-018-0271-3) contains supplementary material, which is available to authorized users.

Impacts of stove/fuel use and outdoor air pollution on chemical composition of household particulate matter

“…56,63 However, exposure to mixtures of PAHs alone does not elicit the same biological responses as the PM extracts containing these PAHs, indicating that the mixture of chemical components in PM is also essential. [66][67][68] Household concentrations of selected transition metals, arsenic, and lead did not exhibit clear trends relative to stove use ( However, environmentally derived trace metal content in biomass varies with biomass species and soil characteristics 72,73 and therefore is not likely to be consistent between regions, biomass types, or even samples. Some of these metals (eg, V, Fe, Mn) may also derive from crustal sources, which can be evaluated by calculating enrichment relative to crustal concentrations.…”

Aromatic hydrocarbon receptors in the immune system: Review and hypotheses

“…Tobacco smoke (in which aromatic hydrocarbons are present) seems to increase the manifestation of lupus [21]. Polychlorinated biphenyls, which are present in frequently consumed human diet (fish, hamburger, and poultry are the most contaminated), increase autoimmunity rates [22] as well as aromatic hydrocarbons present in atmospheric contaminations [23].…”

The Aryl Hydrocarbon Receptor as an Immune-Modulator of Atmospheric Particulate Matter-Mediated Autoimmunity

“…In the context of exposure to PM and its derivatives, O'Driscoll et al (100) demonstrated that exposure to standard reference material (SRM)1650b PM, which is from a 4-cylinder diesel truck engine, enhanced Th17 differentiation in an AHR-dependent manner and SRM2975, which is from a 2-cylinder diesel forklift engine, enhanced Th1 differentiation in an AHR-dependent manner [Figure 1 from O'Driscoll et al (100)]. In addition, the chemically-extracted OF of SRM1650b and SRM2975 which contains AHR ligands, such as PAHs, enhanced Th17 differentiation in an AHR-dependent manner (100). Synthetic PAH mixtures which include 15 PAHs present in SRM1650b and SRM2975 enhanced Th17 differentiation, however SRM1650b synthetic PAH mixture required the AHR at high doses and at lower doses enhanced Th17 differentiation only in the absence of CYP enzymes (100).…”

“…In addition, the chemically-extracted OF of SRM1650b and SRM2975 which contains AHR ligands, such as PAHs, enhanced Th17 differentiation in an AHR-dependent manner (100). Synthetic PAH mixtures which include 15 PAHs present in SRM1650b and SRM2975 enhanced Th17 differentiation, however SRM1650b synthetic PAH mixture required the AHR at high doses and at lower doses enhanced Th17 differentiation only in the absence of CYP enzymes (100). SRM2975 synthetic PAH mixture enhanced Th17 differentiation only in the absence of CYP enzymes suggesting that the inhibition of CYP enzymes prevents the breakdown of the active component allowing for the observed T cell effect [(Figure 1 from O'Driscoll et al (100)] (100).…”

“…Synthetic PAH mixtures which include 15 PAHs present in SRM1650b and SRM2975 enhanced Th17 differentiation, however SRM1650b synthetic PAH mixture required the AHR at high doses and at lower doses enhanced Th17 differentiation only in the absence of CYP enzymes (100). SRM2975 synthetic PAH mixture enhanced Th17 differentiation only in the absence of CYP enzymes suggesting that the inhibition of CYP enzymes prevents the breakdown of the active component allowing for the observed T cell effect [(Figure 1 from O'Driscoll et al (100)] (100). Similarly, O'Driscoll et al (101) demonstrated that an ambient urban dust PM sample enhanced Th17 differentiation in an AHR-dependent manner.…”