Recombinant multimeric dog allergen prevents airway hyperresponsiveness in a model of asthma marked by vigorous TH 2 and TH 17 cell responses
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Recombinant multimeric dog allergen prevents airway hyperresponsiveness in a model of asthma marked by vigorous TH 2 and TH 17 cell responses. / Stark, Julian M; Liu, Jielu; Tibbitt, Christopher A; Christian, Murray; Ma, Junjie; Wintersand, Anna; Dunst, Josefine; Kreslavsky, Taras; Murrell, Ben; Adner, Mikael; Grönlund, Hans; Gafvelin, Guro; Coquet, Jonathan M.
In: Allergy, Vol. 77, No. 10, 10.2022, p. 2987-3001.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Recombinant multimeric dog allergen prevents airway hyperresponsiveness in a model of asthma marked by vigorous TH 2 and TH 17 cell responses
AU - Stark, Julian M
AU - Liu, Jielu
AU - Tibbitt, Christopher A
AU - Christian, Murray
AU - Ma, Junjie
AU - Wintersand, Anna
AU - Dunst, Josefine
AU - Kreslavsky, Taras
AU - Murrell, Ben
AU - Adner, Mikael
AU - Grönlund, Hans
AU - Gafvelin, Guro
AU - Coquet, Jonathan M
N1 - © 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
PY - 2022/10
Y1 - 2022/10
N2 - BACKGROUND: Allergy to dogs affects around 10% of the population in developed countries. Immune therapy of allergic patients with dog allergen extracts has shown limited therapeutic benefit.METHODS: We established a mouse model of dog allergy by repeatedly administering dog dander and epithelium extracts via the intranasal route. We also assessed the efficacy of a recombinant multimeric protein containing Can f 1, f 2, f 4 and f 6 in preventing inflammatory responses to dog extracts.RESULTS: Repeated inhalation of dog extracts induced infiltration of the airways by TH 2 cells, eosinophils and goblet cells, reminiscent of the house dust mite (HDM) model of asthma. Dog extracts also induced robust airway hyperresponsiveness and promoted TH 17 cell responses, which was associated with a high neutrophilic infiltration of the airways. scRNA-Seq analysis of T helper cells in the airways pinpointed a unique gene signature for TH 17 cells. Analysis of T-cell receptors depicted a high frequency of clones that were shared between TH 17, TH 2 and suppressive Treg cells, indicative of a common differentiation trajectory for these subsets. Importantly, sublingual administration of multimeric Can f 1-2-4-6 protein prior to sensitization reduced airway hyperresponsiveness and type 2-mediated inflammation in this model.CONCLUSION: Dog allergen extracts induce robust TH 2 and TH 17 cell-mediated responses in mice. Recombinant Can f 1-2-4-6 can induce tolerance to complex dog allergen extracts.
AB - BACKGROUND: Allergy to dogs affects around 10% of the population in developed countries. Immune therapy of allergic patients with dog allergen extracts has shown limited therapeutic benefit.METHODS: We established a mouse model of dog allergy by repeatedly administering dog dander and epithelium extracts via the intranasal route. We also assessed the efficacy of a recombinant multimeric protein containing Can f 1, f 2, f 4 and f 6 in preventing inflammatory responses to dog extracts.RESULTS: Repeated inhalation of dog extracts induced infiltration of the airways by TH 2 cells, eosinophils and goblet cells, reminiscent of the house dust mite (HDM) model of asthma. Dog extracts also induced robust airway hyperresponsiveness and promoted TH 17 cell responses, which was associated with a high neutrophilic infiltration of the airways. scRNA-Seq analysis of T helper cells in the airways pinpointed a unique gene signature for TH 17 cells. Analysis of T-cell receptors depicted a high frequency of clones that were shared between TH 17, TH 2 and suppressive Treg cells, indicative of a common differentiation trajectory for these subsets. Importantly, sublingual administration of multimeric Can f 1-2-4-6 protein prior to sensitization reduced airway hyperresponsiveness and type 2-mediated inflammation in this model.CONCLUSION: Dog allergen extracts induce robust TH 2 and TH 17 cell-mediated responses in mice. Recombinant Can f 1-2-4-6 can induce tolerance to complex dog allergen extracts.
KW - Allergens
KW - Animals
KW - Asthma
KW - Disease Models, Animal
KW - Dogs
KW - Hypersensitivity/metabolism
KW - Mice
KW - Pyroglyphidae
KW - Respiration Disorders
KW - Respiratory Hypersensitivity/metabolism
KW - Th2 Cells
U2 - 10.1111/all.15399
DO - 10.1111/all.15399
M3 - Journal article
C2 - 35657107
VL - 77
SP - 2987
EP - 3001
JO - Allergy: European Journal of Allergy and Clinical Immunology
JF - Allergy: European Journal of Allergy and Clinical Immunology
SN - 0105-4538
IS - 10
ER -
ID: 356967382