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J Immunol. 2017 Jan 15;198(2):895-907. doi: 10.4049/jimmunol.1601448. Epub 2016 Nov 30.

Allergen-Induced CD4+ T Cell Cytokine Production within Airway Mucosal Dendritic Cell-T Cell Clusters Drives the Local Recruitment of Myeloid Effector Cells.

Author information

1
MediCity Research Laboratory, University of Turku, 20520 Turku, Finland; tibor.veres@utu.fi rgermain@nih.gov.
2
Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
3
MediCity Research Laboratory, University of Turku, 20520 Turku, Finland.
4
Sidra Medical and Research Center, Doha, Qatar.
5
World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan; and.
6
Department of Medical Microbiology and Immunology, University of Turku, 20520 Turku, Finland.
7
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.

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.

PMID:
27903737
PMCID:
PMC5225021
DOI:
10.4049/jimmunol.1601448
[Indexed for MEDLINE]
Free PMC Article

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