title: Urban Particulate Matter-Activated Human Dendritic Cells Induce the Expansion of Potent Inflammatory Th1, Th2, and Th17 Effector Cells.
abstract: Exposure to urban particulate matter (UPM) exacerbates asthmatic lung inflammation. Lung dendritic cells (DCs) are critical for stimulating T cell immunity and in maintaining airway tolerance, but they 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 (Tms), 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 or tetanus toxoid control antigen. 5-(and -6)-Carboxyfluorescein diacetate succinimidyl ester-labeled blood Tms were cocultured 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 Tms isolated from both allergic patients with asthma and healthy control subjects, whereas only IL-13 was produced by Tms from patients with atopic asthma stimulated by house dust mite-loaded DCs. UPM-DCs drove the expansion and differentiation of a mixed population of Th1, Th2, and Th17 cell effectors through a mechanism that was dependent on major histocompatibility class II but not on cytokine-driven expansion. The data suggest that UPM not only has adjuvant properties but is also a source of antigen that stimulates the generation of Th2, Th1, and Th17 effector phenotypes, which have been implicated in both exacerbations of asthma and chronic inflammatory diseases.
authors.affiliation: 1 Division of Asthma, Allergy, and Lung Biology, Medical Research Council-Asthma United Kingdom Centre for Allergic Mechanisms of Asthma, Guy's Hospital, King's College London, London, United Kingdom.
authors.forename: Nick C
authors.initials: NC
authors.lastname: Matthews
authors.affiliation: 1 Division of Asthma, Allergy, and Lung Biology, Medical Research Council-Asthma United Kingdom Centre for Allergic Mechanisms of Asthma, Guy's Hospital, King's College London, London, United Kingdom.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Pfeffer
authors.affiliation: 1 Division of Asthma, Allergy, and Lung Biology, Medical Research Council-Asthma United Kingdom Centre for Allergic Mechanisms of Asthma, Guy's Hospital, King's College London, London, United Kingdom.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Mann
authors.affiliation: 2 Environmental Research Group, Medical Research Council-Public Health England Centre for Environment and Health, Franklin Wilkins Building, King's College London, London, United Kingdom; and.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Kelly
authors.affiliation: 1 Division of Asthma, Allergy, and Lung Biology, Medical Research Council-Asthma United Kingdom Centre for Allergic Mechanisms of Asthma, Guy's Hospital, King's College London, London, United Kingdom.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Corrigan
authors.affiliation: 1 Division of Asthma, Allergy, and Lung Biology, Medical Research Council-Asthma United Kingdom Centre for Allergic Mechanisms of Asthma, Guy's Hospital, King's College London, London, United Kingdom.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Hawrylowicz
authors.affiliation: 1 Division of Asthma, Allergy, and Lung Biology, Medical Research Council-Asthma United Kingdom Centre for Allergic Mechanisms of Asthma, Guy's Hospital, King's College London, London, United Kingdom.|3 Allergy Centre, Hong Kong Sanatorium and Hospital, Hong Kong, People's Republic of China.
authors.forename: Tak H
authors.initials: TH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D052638:Particulate Matter / Q000276:immunology / Q000633:toxicity*; D010641:Phenotype; D039981:Pyroglyphidae / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D013744:Tetanus Toxin / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014504:Urban Health; D055815:Young Adult
chemical_list: D000485:Allergens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D018836:Inflammation Mediators; D052638:Particulate Matter; D011948:Receptors, Antigen, T-Cell; D013744:Tetanus Toxin
keywords: air pollution; cytokines; dendritic cells; memory CD4 T cells; urban particulate matter