IL-17 regulates DC migration to the peribronchial LNs and allergen presentation in experimental allergic asthma
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IL-17 regulates DC migration to the peribronchial LNs and allergen presentation in experimental allergic asthma. / Jirmo, Adan Chari; Busse, Mandy; Happle, Christine; Skuljec, Jelena; Dalüge, Kathleen; Habener, Anika; Grychtol, Ruth; DeLuca, David S; Breiholz, Oliver D; Prinz, Immo; Hansen, Gesine.
in: EUR J IMMUNOL, Jahrgang 50, Nr. 7, 07.2020, S. 1019-1033.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - IL-17 regulates DC migration to the peribronchial LNs and allergen presentation in experimental allergic asthma
AU - Jirmo, Adan Chari
AU - Busse, Mandy
AU - Happle, Christine
AU - Skuljec, Jelena
AU - Dalüge, Kathleen
AU - Habener, Anika
AU - Grychtol, Ruth
AU - DeLuca, David S
AU - Breiholz, Oliver D
AU - Prinz, Immo
AU - Hansen, Gesine
N1 - © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2020/7
Y1 - 2020/7
N2 - IL-17 is associated with different phenotypes of asthma, however, it is not fully elucidated how it influences induction and maintenance of asthma and allergy. In order to determine the role of IL-17 in development of allergic asthma, we used IL-17A/F double KO (IL-17A/F KO) and WT mice with or without neutralization of IL-17 in an experimental allergic asthma model and analyzed airway hyperresponsiveness, lung inflammation, T helper cell polarization, and DCs influx and activation. We report that the absence of IL-17 reduced influx of DCs into lungs and lung draining LNs. Compared to WT mice, IL-17A/F KO mice or WT mice after neutralization of IL-17A showed reduced airway hyperresponsiveness, eosinophilia, mucus hypersecretion, and IgE levels. DCs from draining LNs of allergen-challenged IL-17A/F KO mice showed a reduction in expression of migratory and costimulatory molecules CCR7, CCR2, MHC-II, and CD40 compared to WT DCs. Moreover, in vivo stimulation of adoptively transferred antigen-specific cells was attenuated in lung-draining LNs in the absence of IL-17. Thus, we report that IL-17 enhances airway DC activation, migration, and function. Consequently, lack of IL-17 leads to reduced antigen-specific T cell priming and impaired development of experimental allergic asthma.
AB - IL-17 is associated with different phenotypes of asthma, however, it is not fully elucidated how it influences induction and maintenance of asthma and allergy. In order to determine the role of IL-17 in development of allergic asthma, we used IL-17A/F double KO (IL-17A/F KO) and WT mice with or without neutralization of IL-17 in an experimental allergic asthma model and analyzed airway hyperresponsiveness, lung inflammation, T helper cell polarization, and DCs influx and activation. We report that the absence of IL-17 reduced influx of DCs into lungs and lung draining LNs. Compared to WT mice, IL-17A/F KO mice or WT mice after neutralization of IL-17A showed reduced airway hyperresponsiveness, eosinophilia, mucus hypersecretion, and IgE levels. DCs from draining LNs of allergen-challenged IL-17A/F KO mice showed a reduction in expression of migratory and costimulatory molecules CCR7, CCR2, MHC-II, and CD40 compared to WT DCs. Moreover, in vivo stimulation of adoptively transferred antigen-specific cells was attenuated in lung-draining LNs in the absence of IL-17. Thus, we report that IL-17 enhances airway DC activation, migration, and function. Consequently, lack of IL-17 leads to reduced antigen-specific T cell priming and impaired development of experimental allergic asthma.
KW - Allergens/genetics
KW - Animals
KW - Antigen Presentation
KW - Asthma/genetics
KW - Bronchi/immunology
KW - Cell Movement/genetics
KW - Dendritic Cells/immunology
KW - Interleukin-17/genetics
KW - Lymph Nodes/immunology
KW - Mice
KW - Mice, Knockout
U2 - 10.1002/eji.201948409
DO - 10.1002/eji.201948409
M3 - SCORING: Journal article
C2 - 32142593
VL - 50
SP - 1019
EP - 1033
JO - EUR J IMMUNOL
JF - EUR J IMMUNOL
SN - 0014-2980
IS - 7
ER -