Dataset Information

Ambient urban dust particulate matter reduces pathologic T cells in the CNS and severity of EAE.

ABSTRACT: BACKGROUND:Autoimmune diseases have increased in incidence and prevalence worldwide. While genetic predispositions play a role, environmental factors are a major contributor. Atmospheric particulate matter (PM) is a complex mixture composed of metals, nitrates, sulfates and diverse adsorbed organic compounds like polycyclic aromatic hydrocarbons (PAHs) and dioxins. Exposure to atmospheric PM aggravates autoimmune diseases such as type 1 diabetes, rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus, among others. PAHs and dioxins are known aryl hydrocarbon receptor (AHR) ligands. The AHR modulates T cell differentiation and directs the balance between effector and regulatory T cells in vitro and in experimental autoimmune encephalomyelitis (EAE), a murine model of autoimmune disease. This study aims to identify pathways that contribute to autoimmune disease and their potential use as therapeutic targets to alleviate symptoms and the need for global immunosuppression. This study tests the hypothesis that atmospheric PM enhances effector T cell differentiation and aggravates autoimmune disease. RESULTS:An atmospheric ambient urban dust PM sample, standard reference material (SRM)1649b, was tested for its effects on autoimmunity. SRM1649b PM enhanced Th17 differentiation in an AHR-dependent manner in vitro, however intranasal treatment of SRM1649b PM delayed onset of EAE and reduced cumulative and peak clinical scores. Chronic and acute intranasal exposure of SRM1649b PM delayed onset of EAE. Chronic intranasal exposure did not reduce severity of EAE while acute intranasal exposure significantly reduced severity of disease. Acute intranasal treatment of low dose SRM1649b PM had no effect on clinical score or day of onset in EAE. Delayed onset of EAE by intranasal SRM1649b PM was AHR-dependent in vivo. Oral gavage of SRM1649b PM, in the absence of AHR ligands in the diet, had no effect on day of disease onset or severity of EAE. Day 10 analysis of T cells in the CNS after intranasal treatment of SRM1649b PM showed a reduction of pathologic T cell subsets in vivo. Moreover, MOG-specific splenocytes require AHR to generate or maintain IL-10 producing cells and reduce IFN? producing cells in vitro. CONCLUSIONS:These results identify the AHR pathway as a potential target for driving targeted immunosuppression in the CNS in the context of atmospheric PM-mediated autoimmune disease. The effects of SRM1649b PM on EAE are dependent on route of exposure, with intranasal treatment reducing severity of EAE and delaying disease onset while oral gavage has no effect. Intranasal SRM1649b PM reduces pathologic T cells in the CNS, specifically Th1 cells and Th1Th17 double positive cells, leading to reduced severity of EAE and AHR-dependent delayed disease onset. Additionally, SRM1649b PM treatment of antigen-specific T cells leads to AHR-dependent increase in percent IL-10 positive cells in vitro. These findings may shed light on the known increase of infection after exposure to atmospheric PM and serve as the first step in identifying components of the AHR pathway responsible for Th1-mediated immunosuppression in response to atmospheric PM exposure.

SUBMITTER: O'Driscoll CA

PROVIDER: S-EPMC6263800 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ambient urban dust particulate matter reduces pathologic T cells in the CNS and severity of EAE.

O'Driscoll Chelsea A CA Owens Leah A LA Hoffmann Erica J EJ Gallo Madeline E ME Afrazi Amin A Han Mei M Fechner John H JH Schauer James J JJ Bradfield Christopher A CA Mezrich Joshua D JD

Environmental research 20181001

<h4>Background</h4>Autoimmune diseases have increased in incidence and prevalence worldwide. While genetic predispositions play a role, environmental factors are a major contributor. Atmospheric particulate matter (PM) is a complex mixture composed of metals, nitrates, sulfates and diverse adsorbed organic compounds like polycyclic aromatic hydrocarbons (PAHs) and dioxins. Exposure to atmospheric PM aggravates autoimmune diseases such as type 1 diabetes, rheumatoid arthritis, multiple sclerosis, ...[more]

PMID: 30316103

Similar Datasets

Project description:In this study, we examine the oxidative potential of airborne particulate matter (PM) in Beirut, Lebanon, as influenced by dust events originating in the Sahara and Arabian deserts. Segregated fine (< 2.5 ?m) and coarse (2.5-10 ?m) PM samples collected during dust events, as well as during non-dust periods, were analyzed for chemical composition, and the in vitro alveolar macrophage (AM) assay was utilized to determine the oxidative potential of both types of samples. We performed Spearman rank-order correlation analysis between individual chemical components and the oxidative potential of PM to examine the impact of the changes in PM chemical composition due to the occurrence of dust events on overall PM oxidative potential. Our findings revealed that the oxidative potential of Beirut's urban PM during non-dust periods was much higher than during dust episodes for fine PM. Our findings also indicated that tracers of tailpipe emissions (i.e., elemental (EC) and organic carbon (OC)), non-tailpipe emissions (i.e., heavy metals including Cu, Zn, As, Cd, and Pb), and secondary organic aerosols (SOA) (i.e., water-soluble organic carbon, WSOC) were significantly associated with the oxidative potential of PM during dust days and non-dust periods. However, the contribution of desert dust aerosols to Beirut's indigenous PM composition did not exacerbate its oxidative potential, as indicated by the negative correlations between the oxidative potential of PM and the concentrations of crustal elements that were enriched during the dust days. This suggests that aerosols generated during Saharan and Arabian dust events pose no additional health risk to the population due to PM-triggered reactive oxygen species formation. These results significantly contribute to our understanding of the effects of desert dust aerosols on the composition and oxidative potential of PM in several countries throughout the entire Middle East region that are impacted by dust events in the Sahara and Arabian deserts.

Project description:Murine Pulmonary Responses to Ambient Baltimore Particulate Matter: Genomic Analysis and Contribution to Airway Hyperresponsiveness Asthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Environmental factors such as ambient particulate matter (PM), a major air pollutant, has been demonstrated in epidemiological studies to contribute to asthma exacerbation and increased asthma prevalence. OBJECTIVE: We investigated the genomic and pathophysiological effects of Baltimore PM (median diameter 1.78 µm) in a murine model of asthma to identify potential biomarkers. METHODS: A/J mice with ovalbumin (OVA) –induced AHR were exposed to PM (20 mg/kg, intratracheal), and both AHR and bronchoalveolar lavage (BAL) were assayed on days 1, 4, and 7 post exposure. Lung gene expression profiling (Affymetrix Mouse430_ 2.0) by PM (20 mg/kg, intratracheal) were assayed on OVA- and / or PM--challenged mice. RESULTS: Significant increases of airway responsiveness in OVA-treated mice were observed, indicating an asthmatic phenotype. Ambient PM exposure induced significant changes in AHR in both naive mice and OVA-induced asthmatic mice. In both naive and OVA challenged asthmatic mice, PM induced eosinophil and neutrophil infiltration into airways, elevated BAL protein content, and stimulated secretion of TH1 cytokines (IFN-g, IL-6, and TNF-a) and TH2 cytokines (IL-4, IL-5, and eotaxin) into BAL. Consistent with these results, PM induced expression of genes of innate immune response, chemotaxis and complementary system. CONCLUSION: These studies, consistent with epidemiological data, indicate that PM increases AHR and lung inflammation in naïve mice and exacerbates the asthma phenotype of increased AHR and gene expression pattern changes correlated with acute lung inflammation and airway damage. We used microarrays to detail the global programme of gene expression induced by rhPBEF treatment and VALI. Keywords: gene expression

Dataset Information

Ambient urban dust particulate matter reduces pathologic T cells in the CNS and severity of EAE.

Publications

Ambient urban dust particulate matter reduces pathologic T cells in the CNS and severity of EAE.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets