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:
2013
Lifestage of Participants:
Exposure:
Prenatal; Infant (0-1 year); Youth (1-18 years, specifically 1-2 and 6-18 years of age); Adulthood (18+ years, specifically 18-23 years of age)
Assessment:
Prenatal; Infant (0-1 year); Youth (1-18 years, specifically 1-2 and 6-18 years of age); Adulthood (18+ years, specifically 18-23 years of age)
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:
Allergic disease, specifically food allergy, atopic dermatits, allergic rhinitis, allergic conjunctivitis, and allergic asthma
Respiratory Outcomes:
Asthma
Biological Sample:
Blood; Saliva/buccal cells; Urine
Other Participant Data:
Questionnaire; Spirometry; T cell subsets associated with mechanisms of allergy
Genes or Other DNA Products Studied:
Th2 cytokines, IL-4, IL-13, IFN-ɣ, FoxP3
Epigenetic Mechanisms Studied:
DNA methylation; CpG methylation
Abstract:
Our overall objective is to determine the molecular mechanisms by which immune dysregulation leads to human disease, specifically the atopic diseases of food allergy, allergic rhinitis, allergic conjunctivitis and allergic asthma in the children exposed to high levels of PAHs (polycyclic aromatic hydrocarbons). We previously published work on an important link between PAH exposure in ambient air pollution (AAP) and changes at the DNA level in immune cells that led to their impaired function. This decrease in cell function was directly associated with increases in Th2 cytokines, IL-4 and IL-13, and subsequent clinical outcomes of allergy and asthma, including decreased lung function, in the same pediatric subjects. However, the effect of these cellular changes on allergic disorders was not evaluated at the time; therefore, we will focus on the effects of PAH and will determine whether PAH exposure is associated with systemic immune dysregulation, leading to atopic diseases (food allergy, allergic rhinitis, allergic conjunctivitis, and allergic asthma). T cells are key mediators of the adaptive immune system and play critical roles in modulating inflammation (specifically regulatory T cells or Treg) and inducing allergy (i.e., Th2 effector cells which can lead to isotype switching of B cells to synthesize IgE, a molecule associated with allergies). To date, we have focused our studies on isolated T cell subsets; and, in this proposal, we will conduct studies on Th subsets to be able to elucidate the full mechanisms of how PAHs modulate the immune system. To do this, our approach is to perform a cross-sectional analysis in a well-defined "piece-wise" continuum of all pediatric ages in immune development for whom detailed information will be collected on human disease outcomes and for whom blood, saliva, and urine samples will be collected at repeated time points. We plan to use novel and innovative immunological studies including epigenetic pyrosequencing studies on single cells and mass spectrometry based flow cytometry for detection of 38 simultaneous immune cell parameters. In this way, we will be able to determine key time points of sensitivity of the immune system to PAH exposure by defining the molecular mechanisms that play a role in immune system impairment during immune development.
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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.