PMID- 28063043
OWN - NLM
STAT- MEDLINE
DCOM- 20180131
LR  - 20180426
IS  - 1940-6029 (Electronic)
IS  - 1064-3745 (Linking)
VI  - 1559
DP  - 2017
TI  - Subcutaneous and Sublingual Immunotherapy in a Mouse Model of Allergic Asthma.
PG  - 137-168
LID - 10.1007/978-1-4939-6786-5_11 [doi]
AB  - 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.
FAU - Hesse, Laura
AU  - Hesse L
AD  - 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.
AD  - Groningen Research Institute for Asthma and COPD (GRIAC), University Medical 
      Center Groningen, University of Groningen, Groningen, The Netherlands.
FAU - Nawijn, Martijn C
AU  - Nawijn MC
AD  - 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. M.C.Nawijn@umcg.nl.
AD  - Groningen Research Institute for Asthma and COPD (GRIAC), University Medical 
      Center Groningen, University of Groningen, Groningen, The Netherlands. 
      M.C.Nawijn@umcg.nl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Methods Mol Biol
JT  - Methods in molecular biology (Clifton, N.J.)
JID - 9214969
RN  - 0 (Allergens)
RN  - 0 (Antigens, Plant)
RN  - 0 (Complex Mixtures)
RN  - 0 (Cytokines)
RN  - 0 (Plant Extracts)
RN  - 0 (grass pollen extract, alum-adsorbed)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Allergens/*administration & dosage
MH  - Animals
MH  - Antigens, Plant/*administration & dosage
MH  - Asthma/chemically induced/immunology/pathology/*therapy
MH  - Bronchoalveolar Lavage Fluid/cytology/immunology
MH  - Complex Mixtures/administration & dosage
MH  - Cytokines/biosynthesis
MH  - Disease Models, Animal
MH  - Female
MH  - Flow Cytometry/methods
MH  - Humans
MH  - Hypersensitivity/immunology/pathology/*therapy
MH  - Immune Tolerance/drug effects
MH  - Immunoglobulin E/biosynthesis
MH  - Injections, Subcutaneous/*methods
MH  - Lung/immunology/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Ovalbumin/administration & dosage
MH  - Plant Extracts/*administration & dosage
MH  - Pyroglyphidae/chemistry/immunology
MH  - Sublingual Immunotherapy/*methods
OTO - NOTNLM
OT  - Allergic asthma
OT  - Bronchoalveolar lavage
OT  - Eosinophilia
OT  - FlexiVent
OT  - Flow cytometry
OT  - Grass pollen (GP)
OT  - House dust mite (HDM)
OT  - Mouse model
OT  - Subcutaneous immunotherapy (SCIT)
OT  - Sublingual immunotherapy (SLIT)
EDAT- 2017/01/08 06:00
MHDA- 2018/02/01 06:00
CRDT- 2017/01/08 06:00
PHST- 2017/01/08 06:00 [entrez]
PHST- 2017/01/08 06:00 [pubmed]
PHST- 2018/02/01 06:00 [medline]
AID - 10.1007/978-1-4939-6786-5_11 [doi]
PST - ppublish
SO  - Methods Mol Biol. 2017;1559:137-168. doi: 10.1007/978-1-4939-6786-5_11.