dc.contributor.author | Mann, EH | |
dc.contributor.author | Ho, T-R | |
dc.contributor.author | Pfeffer, PE | |
dc.contributor.author | Matthews, NC | |
dc.contributor.author | Chevretton, E | |
dc.contributor.author | Mudway, I | |
dc.contributor.author | Kelly, FJ | |
dc.contributor.author | Hawrylowicz, CM | |
dc.date.accessioned | 2019-04-09T09:30:39Z | |
dc.date.available | 2019-04-09T09:30:39Z | |
dc.date.issued | 2017-09-01 | |
dc.identifier.issn | 1044-1549 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/56771 | |
dc.description.abstract | Urban particulate matter (UPM) air pollution and vitamin D deficiency are detrimentally associated with respiratory health. This is hypothesized to be due in part to regulation of IL-17A, which UPM is reported to promote. Here, we used a myeloid dendritic cell (DC)-memory CD4+ T cell co-culture system to characterize UPM-driven IL-17A+ cells, investigate the mechanism by which UPM-primed DCs promote this phenotype, and address evidence for cross-regulation by vitamin D. CD1c+ myeloid DCs were cultured overnight with or without a reference source of UPM and/or active vitamin D (1,25[OH]2D3) before they were co-cultured with autologous memory CD4+ T cells. Supernatants were harvested for cytokine analysis on Day 5 of co-culture, and intracellular cytokine staining was performed on Day 7. UPM-primed DCs increased the proportion of memory CD4+ T cells expressing the T helper 17 cell (Th17)-associated cytokines IL-17A, IL-17F, and IL-22, as well as IFN-γ, granulocyte-macrophage colony-stimulating factor, and granzyme B. Notably, a large proportion of the UPM-driven IL-17A+ cells co-expressed these cytokines, but not IL-10, indicative of a proinflammatory Th17 profile. UPM-treated DCs expressed elevated levels of il23 mRNA and increased secretion of IL-23p40. Neutralization of IL-23 in culture reduced the frequency of IL-17A+IFN-γ+ cells without affecting cell proliferation. 1,25(OH)2D3 counteracted the UPM-driven DC maturation and inhibited the frequency of IL-17A+IFN-γ+ cells, most prominently when DCs were co-treated with the corticosteroid dexamethasone, while maintaining antiinflammatory IL-10 synthesis. These data indicate that UPM might promote an inflammatory milieu in part by inducing an IL-23-driven proinflammatory Th17 response. Restoring vitamin D sufficiency may counteract these UPM-driven effects without obliterating important homeostatic immune functions. | en_US |
dc.format.extent | 355 - 366 | |
dc.language | eng | |
dc.language.iso | en | en_US |
dc.publisher | American Thoracic Society | en_US |
dc.relation.ispartof | American Journal of Respiratory Cell and Molecular Biology | |
dc.rights | Originally Published in: Mann EH, Ho TR, Pfeffer PE, Matthews NC, Chevretton E, Mudway I, Kelly FJ, Hawrylowicz CM. Vitamin D counteracts an IL-23–dependent IL-17A+ IFN-γ+ response driven by urban particulate matter. American journal of respiratory cell and molecular biology. 2017 Sep;57(3):355-66. The final publication is available at https://www.atsjournals.org/doi/10.1165/rcmb.2016-0409OC. | |
dc.subject | IL-23 | en_US |
dc.subject | Th17 | en_US |
dc.subject | air pollution | en_US |
dc.subject | corticosteroids | en_US |
dc.subject | vitamin D | en_US |
dc.subject | Calcitriol | en_US |
dc.subject | Cell Differentiation | en_US |
dc.subject | Cities | en_US |
dc.subject | Dendritic Cells | en_US |
dc.subject | Dexamethasone | en_US |
dc.subject | Humans | en_US |
dc.subject | Interferon-gamma | en_US |
dc.subject | Interleukin-17 | en_US |
dc.subject | Interleukin-23 | en_US |
dc.subject | Myeloid Cells | en_US |
dc.subject | Particulate Matter | en_US |
dc.subject | Phenotype | en_US |
dc.subject | Th17 Cells | en_US |
dc.subject | Up-Regulation | en_US |
dc.subject | Vitamin D | en_US |
dc.title | Vitamin D Counteracts an IL-23-Dependent IL-17A+IFN-γ+ Response Driven by Urban Particulate Matter. | en_US |
dc.type | Article | en_US |
dc.rights.holder | Copyright © 2017 by the American Thoracic Society | |
dc.identifier.doi | 10.1165/rcmb.2016-0409OC | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/28463086 | en_US |
pubs.issue | 3 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 57 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |