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,¶
* Division of Pulmonary and Critical Care Medicine,
Division of Infectious Diseases, Department of Medicine,
Department of Environmental Medicine,
Department of Pathology,
¶ Skirball Institute for Biomolecular Medicine, Molecular Pathogenesis Program, New York University School of Medicine, New York, NY 10016; and
|| Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina, Chapel Hill, NC 27599
Increased exposure to air pollutants such as diesel exhaust particles (DEP) has been proposed as one mechanism to explain the rise in allergic disorders. However, the immunologic mechanisms by which DEP enhance allergic sensitization and asthma remain unclear. We hypothesized that DEP act as an adjuvant for immature dendritic cell (DC) maturation via its effect on airway epithelial cell-derived microenvironment for DC. Immature monocyte-derived DC (iMDDC) failed to undergo phenotypic (CD80, CD83, CD86) or functional (T cell activation) maturation in response to exposure to DEP (0.001–100 µg/ml). In contrast, primary cultures of human bronchial epithelial cells (HBEC) treated with DEP induced iMDDC phenotypic maturation (2.6 ± 0.1-fold increase in CD83 expression, n = 4, p < 0.05) and functional maturation (2.6 ± 0.2-fold increase in T cell activation, n = 4, p < 0.05). Functional maturation of iMDDC was induced by conditioned medium derived from DEP-treated HBEC, and was inhibited in cultures with DEP-treated HBEC and blocking Abs against GM-CSF, or GM-CSF-targeted small interfering RNA. These data suggest that DEP induce Ag-independent DC maturation via epithelial cell-DC interactions mediated by HBEC-derived GM-CSF. Although additional signals may be required for polarization of DC, these data suggest a novel mechanism by which environmental pollutants alter airway immune responses.
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