Grantee Research Project Results
Final Report: Ambient Pollutant/Bioaerosol Effects on Treg Function
EPA Grant Number: R834596C003Subproject: this is subproject number 003 , established and managed by the Center Director under grant R834596
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Center for Integrative Research on Childhood Leukemia and the Environment - 2015
Center Director: Metayer, Catherine
Title: Ambient Pollutant/Bioaerosol Effects on Treg Function
Investigators: Tager, Ira , Hammond, S. Katharine , Balmes, John R. , Eisen, Ellen , Nadeau, Kari
Institution: University of California - Berkeley , Stanford University
EPA Project Officer: Callan, Richard
Project Period: May 7, 2010 through May 6, 2013 (Extended to May 6, 2014)
RFA: Children's Environmental Health and Disease Prevention Research Centers: Formative Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
The goal is to further understand the link between indicators of exposure and outcomes on human health by studying immune system changes in subjects exposed to elevated levels of ambient air pollution. The researchers hypothesized that immunological indicators linked to environmental exposure and health outcomes will elucidate the role and mechanism of air pollution in asthma. This link is theoretically understood, circumstantially clear, but not yet proven. The investigators have developed a comprehensive novel indicator of immune function that can be performed on one drop of blood. This method will be used to examine cellular, serological, and epigenetic biomarker changes in peripheral blood that can be broadly applied to an individual health outcome. The objectives of the research were (1) to examine the link between specific immune indicators and ambient air pollution exposures (level of exposure, chronicity of exposure, and type of exposure: ozone, NO, NO2, CO, PM2.5, PM10, elemental carbon, polycyclic aromatic hydrocarbons [PAHs], daily naphthalene, endotoxin) through a database collected in a large population in Fresno, CA; and (2) to characterize the relationship between immune indicators and health outcomes of asthma.
Summary/Accomplishments (Outputs/Outcomes):
Work on the project aims proceeded smoothly and according to project timelines. All subjects have been enrolled in the study, and the researchers have performed all cellular and molecular analyses on the blood samples obtained from the subjects. A manuscript for this project has been published (Hew, et al., CEA 2014).
Significant immunotoxic effects were observed using in vivo and ex vivo studies. The data demonstrated that: 1) DNA methylation of the Foxp3 gene results in decreased FoxP3 protein levels in Treg and that the levels of FoxP3 decrease are associated with increased levels of exposure to polycyclic aromatic hydrocarbons (PAHs); 2) downregulation of chemokine receptor/cognate ligand pairs (CCR8/CCL1) is worsened by exposure to PAH; that decreases in Treg-associated (TGF-α and IL-10) and increases in Th2-associated plasma markers (IL-4 and IL-13) correlate with increased levels of exposure to ambient air pollution; higher degrees of Treg impairment are associated with severity of asthma, and lower levels of Treg immune indicators can be detected in non-asthmatic children exposed to elevated levels of ambient air pollution.
The study results were expected to 1) provide sufficient evidence to help understand the link between the environmental hazard, exposure (individual estimate exposures), and the health outcomes (asthma) through the database collected in a large population in Fresno, CA; and 2) characterize the relationship between ambient air pollution exposure and biomarkers that can be used to indicate the health outcomes of asthma.
Conclusions:
Overall, the project took an innovative approach to investigating whether chronic ambient air exposures, the health outcomes of individual children, and changes in the immune system are correlated. The results are essential for understanding immune mechanisms that could be related to exposure and health outcomes. The results can be used to help decrease and prevent the burden of asthma and allergy, and to reduce exposure to air pollution.
Journal Articles on this Report : 3 Displayed | Download in RIS Format
| Other subproject views: | All 28 publications | 6 publications in selected types | All 6 journal articles |
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| Other center views: | All 50 publications | 15 publications in selected types | All 15 journal articles |
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Hew KM, Walker AI, Kohli A, Garcia M, Syed A, McDonald-Hyman C, Noth EM, Mann JK, Pratt B, Balmes J, Hammond SK, Eisen EA, Nadeau KC. Childhood exposure to ambient polycyclic aromatic hydrocarbons is linked to epigenetic modifications and impaired systemic immunity in T cells. Clinical & Experimental Allergy 2015;45(1):238-248. |
R834596 (2012) R834596 (Final) R834596C003 (Final) R834786 (Final) R835435 (2014) R835435 (2015) R835435 (2016) R835435 (Final) |
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Kohli A, Garcia MA, Miller RL, Maher C, Humblet O, Hammond SK, Nadeau K. Secondhand smoke in combination with ambient air pollution exposure is associated with increased CpG methylation and decreased expression of IFN-γ in T effector cells and Foxp3 in T regulatory cells in children. Clinical Epigenetics 2012;4(1):17 (16 pp.). |
R834596 (2011) R834596 (2012) R834596 (Final) R834596C003 (2011) R834596C003 (2012) R834596C003 (Final) R834786 (2012) R835435 (Final) |
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Liu J, Zhang L, Winterroth LC, Garcia M, Weiman S, Wong JW, Sunwoo JB, Nadeau KC. Epigenetically mediated pathogenic effects of phenanthrene on regulatory T cells. Journal of Toxicology 2013;2013:967029. |
R834596 (2012) R834596 (Final) R834596C003 (2012) R834596C003 (Final) R834786 (2012) R835435 (Final) |
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Supplemental Keywords:
immune function, Foxp3, immune system, epigenetic effects, RFA, Health, Scientific Discipline, ENVIRONMENTAL MANAGEMENT, HUMAN HEALTH, Epidemiology, Health Effects, Biochemistry, Children's Health, Biology, Risk Assessment, asthma, air toxics, prenatal exposure, biological response, measuring childhood exposure, air pollution, assessment of exposure, childhood respiratory disease, children's vulnerablity, harmful environmental agents, developmental disordersRelevant Websites:
CHAPS - SJV: Children's Health & Air Pollution Study - San Joaquin Valley ExitProgress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R834596 Center for Integrative Research on Childhood Leukemia and the Environment - 2015 Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834596C001 Effect of Multi-Level Environmental Exposure on Birth Outcomes
R834596C002 Exposure to Air Pollutants and Risk of Birth Defects
R834596C003 Ambient Pollutant/Bioaerosol Effects on Treg Function
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
6 journal articles for this subproject
Main Center: R834596
50 publications for this center
15 journal articles for this center