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Grantee Research Project Results

NCER Grantee Research Project Results

Ambient Pollutant/Bioaerosol Effects on Treg Function

EPA Grant Number: R834596C003
Subproject: 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: UC Berkeley/Stanford Children’s Environment Health Center
Center Director: Tager, Ira
Title: Ambient Pollutant/Bioaerosol Effects on Treg Function
Investigators: Tager, Ira
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)
Research Category: Children's Health

Description:

Objective:

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 #345]. Some studies have focused on the downstream, unregulated inflammatory responses that result from Th2 polarization associated with ambient air pollution exposure[Bernstein, 2004 #194;Devouassoux, 2002 #55;Diaz-Sanchez, 1999 #60;Diaz-Sanchez, 2000 #58;Diaz-Sanchez, 2000 #57;Diaz-Sanchez, 2005 #188;Diaz-Sanchez, 1996#67;Diaz-Sanchez, 1997 #64;Finkelman, 2004 #53;Fujieda, 1998 #70;Riedl, 2005 #52;Sawant, 2008 #49;Saxon, 2005 #107]. 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 #277]. Treg represent the basic counterregulatory arm of the immune system in human development; however, little is known on how ambient air pollufion 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 #435; Tager, 2006 #72; Tager, 2005 #240; Tager, 1998 #242] in which chronic exposure to ambient air pollution has been measured.

Expected Results:

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 #280; Ono, 2007 #1111 ;Sakaguchi, 2003 #279]. Combined with rigorous epidemiological studies, the innovative functional and molecular tools proposed in project 3 would allow for observafions 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 asthmafic and asthmatic children and Specific Aim 2: to evaluate if Treg dysfunction correlates with esfimate 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 currenfiy 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.

Supplemental Keywords:

ambient air, particulates, oxidants, nitrogen oxides, epidemiology, immunology, causal statistical methods, exposure assessment, asthma, San Joaquin Valley, CA, EPA Region 9;, RFA, Health, Scientific Discipline, ENVIRONMENTAL MANAGEMENT, HUMAN HEALTH, Epidemiology, Biochemistry, Health Effects, Children's Health, Biology, Risk Assessment, asthma, air toxics, prenatal exposure, measuring childhood exposure, biological response, air pollution, children's vulnerablity, assessment of exposure, childhood respiratory disease, harmful environmental agents, developmental disorders


Main Center Abstract and Reports:
R834596    UC Berkeley/Stanford Children’s Environment Health Center

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

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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.

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