Parent Title:
UC Berkeley/Stanford Children's Environmental Health Center
Grant Number:
Principal Investigator:
Nadeau, Kari C
Institution:
University of California, Berkeley
Most Recent Award Year:
2010
Lifestage of Participants:
Exposure:
Youth (1-18 years)
Assessment:
Youth (1-18 years)
Exposures:
Air Pollutants:
Carbon monoxide/carbon dioxide (CO/CO2); Elemental carbon; NO/NO2; NOx; Ozone; Particulate matter (PM2.5, PM10); Polycyclic aromatic hydrocarbons (PAHs)
Health Outcomes:
Immune Outcomes:
Inflammation
Respiratory Outcomes:
Asthma
Biological Sample:
Blood
Other Participant Data:
Questionnaire; Spirometry; T cell subsets associated with mechanisms of allergy
Genes or Other DNA Products Studied:
FOXP3, CCL1, CCR8
Epigenetic Mechanisms Studied:
DNA methylation; CpG methylation
Abstract:
The basic biological mechanisms by which ambient air pollution affects the human body have been studied mainly in the areas of oxidative stress, DNA damage, and airway epithelial changes [Galli, 2008]. Some studies have focused on the downstream, unregulated inflammatory responses that result from Th2 polarization associated with ambient air pollution exposure[Bernstein, 2004;Devouassoux, 2002;Diaz-Sanchez, 1999;Diaz-Sanchez, 2000;Diaz-Sanchez, 2000;Diaz-Sanchez, 2005;Diaz-Sanchez, 1996;Diaz-Sanchez, 1997;Finkelman, 2004;Fujieda, 1998;Riedl, 2005;Sawant, 2008 ;Saxon, 2005]. However, I propose to study the effects of ambient air exposure on Treg, and test the hypothesis that specific decreases in Treg function consequent to this exposure are a major component of the immunopathology of asthma. In fact, the lack of normal Treg function in the lung is associated with asthma in children [HartI, 2007]. Treg represent the basic counterregulatory arm of the immune system in human development; however, little is known on how ambient air pollution affects Treg differentiation and function. My laboratory has performed studies on Treg isolated from blood samples of children living in the Central Valley in collaboration with the Fresno Asthma Children's Environmental Study (FACES) [Margolis, 2008; Tager, 2006; Tager, 2005; Tager, 1998] in which chronic exposure to ambient air pollution has been measured. I have found that Treg function is attenuated by up to 10 fold compared to controls; in addition, this impairment is associated with direct decreases in Foxp3, a gene associated with Treg development and function in humans [Hori, 2003; Ono, 2007; Sakaguchi, 2003]. Combined with rigorous epidemiological studies, the innovative functional and molecular tools proposed in Project 3 would allow for observations about environmental exposure in children to become more fundamental at the basic science level. Specifically, 1 propose: Specific Aim 1 to define the mechanisms of Treg impairment in non asthmatic and asthmatic children and Specific Aim 2: to evaluate if Treg dysfunction correlates with estimate individual exposure. The study will generate a unique body of scientific knowledge of detailed exposure and individual follow-up data linked to immune system changes that are otherwise not currently available to advance the field of environmental effects on health. Our approach will address the biologic plausibility of the association between the increase in asthma and ambient air pollution exposure.
ExpandCollapse Abstract
Related NIEHS-Funded Study Populations
Children's Health and Air Pollution Study (CHAPS)
Principal Investigator:
Hammond, Katharine; Balmes, John; Nadeau, Kari; Shaw, Gary
| Study Population Page Study Population c31
Institution:
University of California, Berkeley and Stanford University
Location:
San Joaquin Valley, California
Number of Participants::
~625
Brief Description::
This prospective study examines how exposure to air pollution influences allergic and metabolic disease risk in children and young adults. The study has enrolled over 600 participants living in the San Joaquin Valley region in central California.