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Urban Particulate Matter-activated Human Dendritic Cells Induce the Expansion of Potent Inflammatory Th1, Th2 and Th17 Effector Cells

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)250-262
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume54
Issue number2
Early online date21 Jul 2015
DOIs
Publication statusE-pub ahead of print - 21 Jul 2015

King's Authors

Abstract

Exposure to urban particulate matter (UPM) exacerbates asthmatic lung inflammation, but suppresses lung immunity to infections. Lung dendritic cells (DCs) are critical for stimulating T-cell immunity and in maintaining airway tolerance, but also react to airway UPM. The adjuvant role of UPM in enhancing primary immune responses by naive cells to allergen has been reported, but the direct effects of UPM-activated DCs on the functionality of human memory CD4 T-cells, which constitute the majority of T-cells in the lung, has not been investigated. Blood CD1c+ DCs were purified and activated with UPM in the presence or absence of house dust mite (HDM), or tetanus toxoid control antigen (TT). CFSE-labelled blood memory CD4 T cells (Tm) were co-cultured with autologous DCs, T-cell proliferation and effector function were assessed using flow cytometry and secreted cytokines were measured by combined bead array. UPM-DCs elicited IFN-γ and IL-13 secretion and induced proliferation in Tm isolated from both allergic asthma patients and healthy controls, whereas only IL-13 was produced by Tm from atopic asthmatics stimulated by HDM-loaded DCs. UPM-DCs drove the expansion and differentiation of a mixed population of Th1, Th2 and Th17 cells effectors through a mechanism that was dependent on MHC-class II not on cytokine-driven expansion. The data suggest that UPM not only has adjuvant properties, but is also a source of antigen that stimulated the generation of Th2, Th1 and Th17 effector phenotypes, which have been implicated in both exacerbations of asthma and chronic inflammatory diseases.

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