title: Allergen-Induced CD4+ T Cell Cytokine Production within Airway Mucosal Dendritic Cell-T Cell Clusters Drives the Local Recruitment of Myeloid Effector Cells.
abstract: Allergic asthma develops in the mucosal tissue of small bronchi. At these sites, local cytokine production by Th2/Th17 cells is believed to be critical for the development of tissue eosinophilia/neutrophilia. Using the mouse trachea as a relevant model of human small airways, we performed advanced in vivo dynamic and in situ static imaging to visualize individual cytokine-producing T cells in the airway mucosa and to define their immediate cellular environment. Upon allergen sensitization, newly recruited CD4+T cells formed discrete Ag-driven clusters with dendritic cells (DCs). Within T cell-DC clusters, a small fraction of CD4+T cells produced IL-13 or IL-17 following prolonged Ag-specific interactions with DCs. As a result of local Th2 cytokine signaling, eosinophils were recruited into these clusters. Neutrophils also infiltrated these clusters in a T cell-dependent manner, but their mucosal distribution was more diffuse. Our findings reveal the focal nature of allergen-driven responses in the airways and define multiple steps with potential for interference with the progression of asthmatic pathology.
authors.affiliation: MediCity Research Laboratory, University of Turku, 20520 Turku, Finland; tibor.veres@utu.fi rgermain@nih.gov.|Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Tibor Z
authors.identifier: 0000-0002-6980-8900
authors.initials: TZ
authors.lastname: Veres
authors.affiliation: MediCity Research Laboratory, University of Turku, 20520 Turku, Finland.
authors.forename: Tamás
authors.initials: T
authors.lastname: Kopcsányi
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.|Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Nicholas
authors.initials: N
authors.lastname: van Panhuys
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Gerner
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Zhiduo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: MediCity Research Laboratory, University of Turku, 20520 Turku, Finland.
authors.forename: Pia
authors.identifier: 0000-0003-1638-5075
authors.initials: P
authors.lastname: Rantakari
authors.affiliation: MediCity Research Laboratory, University of Turku, 20520 Turku, Finland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Dunkel
authors.affiliation: MediCity Research Laboratory, University of Turku, 20520 Turku, Finland.|World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan; and.
authors.forename: Masayuki
authors.identifier: 0000-0001-6122-5201
authors.initials: M
authors.lastname: Miyasaka
authors.affiliation: MediCity Research Laboratory, University of Turku, 20520 Turku, Finland.|Department of Medical Microbiology and Immunology, University of Turku, 20520 Turku, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Salmi
authors.affiliation: MediCity Research Laboratory, University of Turku, 20520 Turku, Finland.|Department of Medical Microbiology and Immunology, University of Turku, 20520 Turku, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
authors.affiliation: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; tibor.veres@utu.fi rgermain@nih.gov.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Germain
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D020545:Respiratory Mucosa / Q000276:immunology
chemical_list: D016207:Cytokines