期刊
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
卷 50, 期 2, 页码 281-291出版社
AMER THORACIC SOC
DOI: 10.1165/rcmb.2012-0465OC
关键词
dendritic cells; CD4 T cells; air pollution; cytokines; urban particulate matter
资金
- Him Lee Fund
- Lee Iu Cheung Fund
- Santander Foundation
- Department of Health via the National Institute for Health Research (NIHR) Clinical Research Facility at Guy's & St Thomas' NHS Foundation Trust
- King's College London
- Asthma UK [MRC-AsthmaUKCentre, 08/019] Funding Source: researchfish
- Medical Research Council [G0801056, G1000758B, G1000758] Funding Source: researchfish
- Natural Environment Research Council [NE/I008039/1] Funding Source: researchfish
- MRC [G0801056] Funding Source: UKRI
- NERC [NE/I008039/1] Funding Source: UKRI
Urban particulate matter (UPM) exacerbates asthmatic lung inflammation and depresses lung immunity. Lung dendritic cells (DCs) react to airway particulates, and have a critical role in linking innate and adaptive immunity, but the direct effects of UPM on DCs, that have been activated by granulocyte/macrophage colony-stimulating factor (GM-CSF), a product of stimulated normal human bronchial epithelial cells, has not been investigated. Human blood CD1c(+) DCs were purified and activated with UPM in the presence or absence of GM-CSF with and without LPS, and DC maturation was assessed by flow cytometry. DC stimulatory capacity and priming of 5-(and -6)-carboxyfluorescein diacetate succinimidyl ester-labeled naive CD4 T cells was investigated using the allogeneic mixed lymphocyte reaction. T cell proliferation and effector function were assessed using flow cytometry and secreted cytokines were measured by combined bead array. UPM enhanced DC maturation in an LPS-independent manner. DCs activated by UPM plus GM-CSF (UPM + GM-CSF DCs) induced higher naive CD4 T cell proliferation in the allogeneic mixed lymphocyte reaction than DCs pretreated by GM-CSF alone (GM-CSF DCs), and elicited both substantially lower levels of IFN-gamma, IL-13, and IL-5 secretion, and lower frequencies of alloantigen-specific T helper (Th) type 1 effector cells than naive CD4 T cells primed by GM-CSF DCs. UPM-stimulated DCs produced IL-6 and TNF-alpha. Neutralization of IL-6 decreased naive CD4 T cell proliferation stimulated by UPM + GM-CSF DCs, and significantly increased the frequency of alloantigen-specific Th1 effector cells, but did not reverse UPM-induced inhibition of IFN-gamma secretion. We conclude that UPM enhances GM-CSF-induced DC maturation and stimulatory capacity, but inhibits the generation of Th1 cells. Thus, UPM exposure may impair Th1 responses to pulmonary pathogens.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据