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Inflammation pp 137–168Cite as

Subcutaneous and Sublingual Immunotherapy in a Mouse Model of Allergic Asthma

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1559))

Abstract

Allergic asthma, caused by inhaled allergens such as house dust mite or grass pollen, is characterized by reversible airway obstruction, associated with an eosinophilic inflammation of the airways, as well as airway hyper responsiveness and remodeling. The inhaled allergens trigger a type-2 inflammatory response with involvement of innate lymphoid cells (ILC2) and Th2 cells, resulting in high production of immunoglobulin E (IgE) antibodies. Consequently, renewed allergen exposure results in a classic allergic response with a distinct early and late phase, both resulting in bronchoconstriction and shortness of breath. Allergen specific immunotherapy (AIT) is the only treatment that is capable of modifying the immunological process underlying allergic responses including allergic asthma and both subcutaneous AIT (SCIT) as well as sublingual AIT (SLIT) have proven clinical efficacy in long term suppression of the allergic response. Although these treatments are very successful for rhinitis, application of AIT in asthma is hampered by variable efficacy, long duration of treatment, and the risk of severe side-effects. A more profound understanding of the mechanisms by which AIT achieves tolerance to allergens in sensitized individuals is needed to improve its efficacy. Mouse models have been very valuable as a preclinical model to characterize the mechanisms of desensitization in AIT and to evaluate novel approaches for improved efficacy. Here, we present a rapid and reproducible mouse model for allergen-specific immunotherapy. In this model, mice are sensitized with two injections of allergen absorbed to aluminum hydroxide to induce allergic sensitization, followed by subcutaneous injections (SCIT) or sublingual administrations (SLIT) of the allergen as immunotherapy treatment. Finally, mice are challenged by three intranasal allergen administrations. We will describe the protocols as well as the most important read-out parameters including measurement of invasive lung function measurements, serum immunoglobulin levels, isolation of broncho-alveolar lavage fluid (BALF), and preparation of cytospins. Moreover, we describe how to restimulate lung single cell suspensions, perform flow cytometry measurements to identify populations of relevant immune cells, and perform ELISAs and Luminex assays to measure the cytokine concentrations in BALF and lung tissue.

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Acknowledgments

Laura Hesse is supported by the Dutch Lung Foundation (NAF10.060).

Author information

Authors and Affiliations

  1. Department of Pathology and Medical Biology, Laboratory of Experimental Pulmonology and Inflammation Research (EXPIRE), University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA52/T2.212), 9713 GZ, Groningen, The Netherlands

    Laura Hesse & Martijn C. Nawijn

  2. Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Laura Hesse & Martijn C. Nawijn

Authors
  1. Laura Hesse
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  2. Martijn C. Nawijn
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Correspondence to Martijn C. Nawijn .

Editor information

Editors and Affiliations

  1. Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

    Björn E. Clausen

  2. Section Medical Physiology Department of Neuroscience, University of Groningen University Medical Center Groningen, Groningen, The Netherlands

    Jon D. Laman

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Hesse, L., Nawijn, M.C. (2017). Subcutaneous and Sublingual Immunotherapy in a Mouse Model of Allergic Asthma. In: Clausen, B., Laman, J. (eds) Inflammation. Methods in Molecular Biology, vol 1559. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6786-5_11

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  • DOI: https://doi.org/10.1007/978-1-4939-6786-5_11

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