IL-17 regulates DC migration to the peribronchial LNs and allergen presentation in experimental allergic asthma

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 -