Pro-oxidative diesel exhaust particle chemicals inhibit LPS-induced dendritic cell responses involved in T-helper differentiation

Ray Chun Fai Chan, Meiying Wang, Ning Li, Yoshiki Yanagawa, Kazunori Onoé, James J. Lee, Andre E. Nel

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Background: Epidemiologic studies show that exposure to ambient particulate matter leads to asthma exacerbation. Diesel exhaust particles (DEPs), a model pollutant, act as an adjuvant for allergic sensitization. Increasing evidence shows that this effect could be mediated by an effect on dendritic cells (DCs). Objective: Our aim was to elucidate the mechanism by which pro-oxidative DEP chemicals change DC function so that these antigen-presenting cells strengthen the immune response to an experimental allergen. Methods: We exposed murine bone marrow-derived DCs and a homogeneous myeloid DC line, BC1, to DEPs and organic extracts made from these particles to determine how the induction of oxidative stress affects cellular maturation, cytokine production, and activation of antigen-specific T cells. Results: DEP extracts induced oxidative stress in DCs. This change in redox equilibrium interfered in the ability of Toll-like receptor agonists to induce the expression of maturation receptors (eg, CD86, CD54, and I-A d) and IL-12 production. This perturbation of DC function was accompanied by decreased IFN-γ and increased IL-10 induction in antigen-specific T cells. The molecular basis for the perturbation of DC function is the activation of a nuclear factor-erythroid 2 (NF-E2)-related factor 2-mediated signaling pathway that suppresses IL-12 production. NF-E2-related factor 2 deficiency abrogates the perturbation of DC function by DEPs. Conclusion: These data provide the first report that pro-oxidative DEP chemicals can interfere in T H1-promoting response pathways in a homogeneous DC population and provide a novel explanation for the adjuvant effect of DEPs on allergic inflammation. Clinical implications: These data clarify the adjuvant effect of particulate air pollutants in allergic inflammatory disease.

Original languageEnglish (US)
Pages (from-to)455-465
Number of pages11
JournalJournal of Allergy and Clinical Immunology
Volume118
Issue number2
DOIs
StatePublished - Aug 2006

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Vehicle Emissions
Dendritic Cells
Particulate Matter
Interleukin-12
Oxidative Stress
CD27 Antigens
Toll-Like Receptors
Antigen-Presenting Cells
Myeloid Cells
Interleukin-10
Allergens
Oxidation-Reduction
Epidemiologic Studies
Asthma
Bone Marrow
Cytokines
Inflammation
T-Lymphocytes
Antigens
Cell Line

Keywords

  • cell differentiation
  • Dendritic cells
  • LPS
  • T 1/T 2 cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Pro-oxidative diesel exhaust particle chemicals inhibit LPS-induced dendritic cell responses involved in T-helper differentiation. / Chan, Ray Chun Fai; Wang, Meiying; Li, Ning; Yanagawa, Yoshiki; Onoé, Kazunori; Lee, James J.; Nel, Andre E.

In: Journal of Allergy and Clinical Immunology, Vol. 118, No. 2, 08.2006, p. 455-465.

Research output: Contribution to journalArticle

Chan, Ray Chun Fai ; Wang, Meiying ; Li, Ning ; Yanagawa, Yoshiki ; Onoé, Kazunori ; Lee, James J. ; Nel, Andre E. / Pro-oxidative diesel exhaust particle chemicals inhibit LPS-induced dendritic cell responses involved in T-helper differentiation. In: Journal of Allergy and Clinical Immunology. 2006 ; Vol. 118, No. 2. pp. 455-465.
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AU - Nel, Andre E.

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AB - Background: Epidemiologic studies show that exposure to ambient particulate matter leads to asthma exacerbation. Diesel exhaust particles (DEPs), a model pollutant, act as an adjuvant for allergic sensitization. Increasing evidence shows that this effect could be mediated by an effect on dendritic cells (DCs). Objective: Our aim was to elucidate the mechanism by which pro-oxidative DEP chemicals change DC function so that these antigen-presenting cells strengthen the immune response to an experimental allergen. Methods: We exposed murine bone marrow-derived DCs and a homogeneous myeloid DC line, BC1, to DEPs and organic extracts made from these particles to determine how the induction of oxidative stress affects cellular maturation, cytokine production, and activation of antigen-specific T cells. Results: DEP extracts induced oxidative stress in DCs. This change in redox equilibrium interfered in the ability of Toll-like receptor agonists to induce the expression of maturation receptors (eg, CD86, CD54, and I-A d) and IL-12 production. This perturbation of DC function was accompanied by decreased IFN-γ and increased IL-10 induction in antigen-specific T cells. The molecular basis for the perturbation of DC function is the activation of a nuclear factor-erythroid 2 (NF-E2)-related factor 2-mediated signaling pathway that suppresses IL-12 production. NF-E2-related factor 2 deficiency abrogates the perturbation of DC function by DEPs. Conclusion: These data provide the first report that pro-oxidative DEP chemicals can interfere in T H1-promoting response pathways in a homogeneous DC population and provide a novel explanation for the adjuvant effect of DEPs on allergic inflammation. Clinical implications: These data clarify the adjuvant effect of particulate air pollutants in allergic inflammatory disease.

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