Effects of sublingual immunotherapy in a murine asthma model sensitized by intranasal administration of house dust mite extracts

Shima, Kenjiro; Koya, Toshiyuki; Tsukioka, Keisuke; Sakagami, Takuro; Hasegawa, Takashi; Fukano, Chiharu; Ohashi-Doi, Katsuyo; Watanabe, Satoshi; Suzuki, Eiichi; Kikuchi, Toshiaki

doi:10.1016/j.alit.2016.05.012

Cited by 15 publications

(17 citation statements)

References 25 publications

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“…Experimental mouse models of HDM‐SLIT treatment have rendered variable results regarding the efficiency of suppressing the different parameters of allergic airway disease, but generally show limited induction of neutralizing antibody responses, in line with our own results. For instance, in one study using Dermatophagoides farinae (Der f) extracts, SLIT treatment had a more pronounced effect on AHR than on Th2‐driven, eosinophilic airway inflammation . In contrast, a study using both Dermatophagoides pteronyssinus (Der p) and Der f extracts showed a stronger effect on suppression of eosinophilic airway inflammation, while AHR was only suppressed at higher doses of extracts used for SLIT treatment .…”

Section: Discussionmentioning

confidence: 99%

Subcutaneous immunotherapy suppresses Th2 inflammation and induces neutralizing antibodies, but sublingual immunotherapy suppresses airway hyperresponsiveness in grass pollen mouse models for allergic asthma

Hesse

Brouwer

Petersen

et al. 2018

Clin Experimental Allergy

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In conclusion, GP-SCIT suppresses Th2 inflammation and induced neutralizing antibodies, while GP-SLIT suppresses the clinically relevant lung function parameters in an asthma mouse model, indicating that the two application routes depend on partially divergent mechanisms of tolerance induction. Interestingly, these data mirror observations in clinical studies, underscoring the translational value of these mouse models.

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Section: Discussionmentioning

confidence: 99%

Subcutaneous immunotherapy suppresses Th2 inflammation and induces neutralizing antibodies, but sublingual immunotherapy suppresses airway hyperresponsiveness in grass pollen mouse models for allergic asthma

Hesse

Brouwer

Petersen

et al. 2018

Clin Experimental Allergy

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“…A plethora of animal models for specific allergen immunotherapy tried optimizing the application mode and route of allergen, by entrapment in tolerogenic PLG particles [46 ▪▪ ], or application concomitantly with CpG [45], probiotics or Vitamin D3 (Table 1) [37–39,41,42 ▪ ,43 ▪▪ ,44,45,46 ▪▪ ,49 ▪ ,51]. In particular, epicutaneous application has achieved promising results without adjuvants [43 ▪▪ ].…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, highly sensitized mice required higher sublingual immunotherapy (SLIT) dose than less sensitized mice to improve airway hyperresponsiveness [37]. Moreover, upon SLIT treatment, a lower proportion of CD4-CD8 γδ cells and a higher frequency of CD8 + CD25 + IFNγ + T cells accompanied by reduced inflammatory responses in the lung were observed [38].…”

Section: Immunomodulation By Allergen-specific Immunotherapymentioning

confidence: 99%

Outstanding animal studies in allergy II. From atopic barrier and microbiome to allergen-specific immunotherapy

Jensen‐Jarolim

Pali‐Schöll

Roth‐Walter

2017

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of reviewAnimal studies published within the past 18 months were assessed, focusing on innate and specific immunomodulation, providing knowledge of high translational relevance for human atopic and allergic diseases.Recent findingsAllergic companion animals represent alternative models, but most studies were done in mice. Atopic dermatitis mouse models were refined by the utilization of cytokines like IL-23 and relevant skin allergens or enzymes. A novel IL-6 reporter mouse allows biomonitoring of inflammation. Both skin pH and the (transferable) microflora have a pivotal role in modulating the skin barrier. The microflora of the gastrointestinal mucosa maintains tolerance to dietary compounds and can be disturbed by antiacid drugs. A key mouse study evidenced that dust from Amish households, but not from Hutterites protected mice against asthma. In studies on subcutaneous and sublingual allergen-specific immunotherapy, much focus was given on delivery and adjuvants, using poly-lacto-co-glycolic particles, CpGs, probiotics or Vitamin D3. The epicutaneous and intralymphatic routes showed promising results in mice and horses in terms of prophylactic and therapeutic allergy treatment.SummaryIn atopic dermatitis, food allergies and asthma, environmental factors, together with the resident microflora and barrier status, decide on sensitization versus tolerance. Also allergen-specific immunotherapy operates with immunomodulatory principles.

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“…Concentrations of Der f 1 and Der f 2 were 4.8 μg/mg extract and 4.0 μg/mg extract, respectively [27]. We measured lipopolysaccharide (LPS) concentrations of Df extract by using an endotoxin-specific chromogenic Limulus test (Endospecy test, Seikagaku Corporation, Tokyo, Japan) in this study and found that the LPS concentration of Df extract at 1,000 ng/mL was 10.7 ± 0.9 pg/mL ( n = 8).…”

Section: Methodsmentioning

confidence: 99%

“…Df was collected and a dried extract prepared as described previously [27]. Concentrations of Der f 1 and Der f 2 were 4.8 μg/mg extract and 4.0 μg/mg extract, respectively [27].…”

Section: Methodsmentioning

confidence: 99%

Dermatophagoides farinae Upregulates the Effector Functions of Eosinophils through αMβ2-Integrin and Protease-Activated Receptor-2

Ueda¹,

Nakagome²,

Kobayashi³

et al. 2019

Int Arch Allergy Immunol

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Background: Even in subjects who are not sensitized to house dust mite (HDM), allergic symptoms can be aggravated by exposure to dust, suggesting that innate immune responses may be involved in these processes. Since eosinophils express pattern recognition receptors, HDM may directly upregulate eosinophil functions through these re ceptors. The objective of this study was to examine whether Dermatophagoides farinae (Df), a representative HDM, or Der f 1, a major allergen of Df, modifies the effector functions of eosinophils. Methods: Eosinophils isolated from the blood of healthy donors or allergic patients were stimulated with Df extract or Der f 1, and their adhesion to recombinant human intercellular adhesion molecule (ICAM)-1 was measured using eosinophil peroxidase assays. Generation of the eosinophil superoxide anion (O₂^–) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) concentrations in cell media were measured by ELISA as a marker of degranulation. Results: Df extract or Der f 1 directly induced eosinophil adhesion to ICAM-1, O₂^– generation, and EDN release. Anti-αM- or anti-β₂-integrin antibodies or protease-activated receptor (PAR)-2 antagonists suppressed the eosinophil adhesion, O₂^– generation, and EDN release induced by Df extract or Der f 1. Eosinophils from allergic patients showed higher adhesion to ICAM-1 than those from healthy donors. Conclusions: These findings suggested that Df extract and Der f 1 directly activate eosinophil functions through αMβ₂-integrin and PAR-2. Eosinophil activation by HDM may play roles in the aggravation of allergic symptoms, not only in HDM-sensitized patients, but also in nonsensitized patients.

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Effects of sublingual immunotherapy in a murine asthma model sensitized by intranasal administration of house dust mite extracts

Abstract: These data suggest that earlier induction of SLIT in HDM-sensitized mice provides superior suppression of AHR and goblet cell metaplasia. The modulation of allergen specific IgG2a and local IgA might play a role in the amelioration of AHR and airway inflammation.

Cited by 15 publications

References 25 publications

Subcutaneous immunotherapy suppresses Th2 inflammation and induces neutralizing antibodies, but sublingual immunotherapy suppresses airway hyperresponsiveness in grass pollen mouse models for allergic asthma

Subcutaneous immunotherapy suppresses Th2 inflammation and induces neutralizing antibodies, but sublingual immunotherapy suppresses airway hyperresponsiveness in grass pollen mouse models for allergic asthma

Outstanding animal studies in allergy II. From atopic barrier and microbiome to allergen-specific immunotherapy

<b><i>Dermatophagoides farinae</i></b> Upregulates the Effector Functions of Eosinophils through αMβ<sub>2</sub>-Integrin and Protease-Activated Receptor-2

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