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.
Highlights
Exposure to particulate matter (PM) has been associated with increased incidence and severity of autoimmune disease
Diesel exhaust PM samples worsen EAE in vivo Previously, our lab published that an ambient urban dust PM, SRM1649b, could enhance Th17 differentiation in vitro in an aryl hydrocarbon receptor (AHR)-dependent manner and in vivo [44]
Given this and that Th17 cells are central to the mechanism of many autoimmune disorders [45, 59,60,61,62,63,64,65], two additional standard reference materials (SRMs) were obtained from diesel exposures: SRM1650b (4-cylinder truck engine diesel) and SRM2975 (2-cylinder forklift engine diesel)
Summary
Exposure to particulate matter (PM) has been associated with increased incidence and severity of autoimmune disease. Diesel PM is a complex mixture composed of an elemental carbon core and adsorbed organic compounds as well as small amounts of sulfates, nitrates, metals, and other trace elements [25]. The diverse primary emission sources and secondary chemical reactions that generate atmospheric PM components lead to complex mixtures of PM components that include metals, nitrates, sulfates and diverse organic compounds like PAHs [30, 31]. This complexity of real world PM makes pinpointing the pathologically significant components of PM difficult to elucidate
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