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

Hesse, Laura; Brouwer, Uilke; Petersen, Arjen H.; Gras, R.; Bosman, Lisette J.; Brimnes, Jens; Elberink, J. N. G. Oude; Oosterhout, Antoon J. M. van; Nawijn, Martijn C.

doi:10.1111/cea.13169

Cited by 16 publications

(28 citation statements)

References 46 publications

(124 reference statements)

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“…Before and after SIT treatments, an ear-swelling test (EST) was performed to evaluate the early phase response to GP to test for allergic sensitization. Herein 10 μL of PBS is injected intradermal in the left ear as a control and 1kSQ of GP in 10 μL is injected in the right ear of mice under isoflurane/oxygen anesthesia 14,15 . After 2 h, ear thickness was measured using a digimatic force-micrometer at 0.5 N ( ± 0.15 N, Mitutoyo, Japan) and the net GP-induced swelling (Δ, in µm) was calculated by subtracting the thickness of the left ear from the right ear.…”

Section: Methodsmentioning

confidence: 99%

“…Blood was collected in MiniCollect serum tubes (Greiner Bio-One, Alphen a/d Rijn, The Netherlands) at several time points via orbital puncture (pre-sera) and after the experiment via the vena cava inferior (post-sera, Figs. 1A and 4A) 14 .…”

Section: Group Sensitisationmentioning

confidence: 98%

“…developed an experimental mouse model for GP-SCIT and GP-SLIT using a single allergen extract, effectively allowing side-by-side comparison 14 . Here, we aimed to study the efficacy of 10 ng VitD3 supplementation in GP-SCIT and GP-SLIT for suppression of asthmatic manifestations upon GP challenges (Figs.…”

Section: Vitd3 Supplementation Enhances Specific Igg2a Responses Indumentioning

confidence: 99%

“…We have previously studied SCIT and SLIT using grass pollen (GP) and directly compared the two treatment regimens 14 . Here, we employed this experimental model of side-by-side subcutaneous and sublingual AIT to directly compare the efficacy of VitD3 as an adjuvant between SCIT and SLIT treatments.…”

mentioning

confidence: 99%

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1,25(OH)2VitD3 supplementation enhances suppression of grass pollen-induced allergic asthma by subcutaneous and sublingual immunotherapy in a mouse model

Hesse

Petersen

Elberink

et al. 2020

Sci Rep

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Allergen specific immunotherapy (AIT) can provide long-term alleviation of symptoms for allergic disease but is hampered by suboptimal efficiency. We and others have previously shown that 1,25(OH)2-VitaminD3 (VitD3) can improve therapeutic efficacy of AIT. However, it is unknown whether VitD3 supplementation has similar effects in sublingual and subcutaneous immunotherapy. Therefore, we aimed to test VitD3 supplementation in both grass pollen (GP) subcutaneous-IT (SCIT) and sublingual-IT (SLIT) in a mouse model for allergic airway inflammation. To this end, GP-sensitized BALB/c mice received GP-SCIT or GP-SLIT with or without 10 ng VitD3, followed by intranasal GP challenges and measurement of airway hyperresponsiveness (AHR) and inflammation. VitD3 supplementation of GP-SCIT resulted in enhanced induction of GP-specific (sp)-IgG2a and suppression of spIgE after challenge. In addition, eosinophil numbers were reduced and levels of IL10 and Amphiregulin were increased in lung tissue. In GP-SLIT, VitD3 supplementation resulted in enhanced sp-IgG2a levels in serum, enhanced suppression of eosinophils and increased IL10 levels in lung tissue, as well as suppression of AHR to methacholine. These data show that VitD3 increases efficacy of both SCIT and SLIT, by enhancing induction of blocking antibodies and suppression of airway inflammation, underscoring the relevance of proficient VitD3 levels for successful AIT. Successful allergen-specific immunotherapy (AIT) induces an immunologic state of tolerance towards allergens and represents a disease-modifying treatment for allergic airway diseases, such as asthma and rhinitis 1,2. AIT is a unique form of therapy wherein allergens are administered via the subcutaneous (SCIT) or sublingual route (SLIT) to render long term relief of symptoms 3,4. The immunological mechanisms include early mast cell and basophil desensitization, inhibition of eosinophilic inflammation, induction of blocking antibodies, suppression of numbers and activity of allergen-specific Th2 cells and type 2 innate lymphoid cells (ILC2s), increases in regulatory T cells (Treg) and their associated cytokines, such as IL10 and TGF-β1 3-5. However, AIT regimes are hampered by low efficacy to suppress some clinical features of allergic airway inflammation, such as bronchial hyperresponsiveness. Moreover, the use of allergen vaccines with IgE-crosslinking capacity has safety concerns 6. To overcome the urgent need for improved AIT efficacy, ideally at lower allergen doses, several strategies have been explored 7 , including the use of adjuvants. We have previously shown the successful use of 1,25-dihydroxy-vitamin D3 (VitD3) as an adjuvant for AIT in the classical mouse model of ovalbumin-induced allergic airway inflammation 8. The physiologically active form of VitD3 binds to the VitD3 receptor (VDR), a nuclear hormone receptor, to exert its immunoregulatory

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Section: Methodsmentioning

confidence: 99%

Section: Group Sensitisationmentioning

confidence: 98%

Section: Vitd3 Supplementation Enhances Specific Igg2a Responses Indumentioning

confidence: 99%

mentioning

confidence: 99%

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1,25(OH)2VitD3 supplementation enhances suppression of grass pollen-induced allergic asthma by subcutaneous and sublingual immunotherapy in a mouse model

Hesse

Petersen

Elberink

et al. 2020

Sci Rep

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show abstract

“…To test our hypothesis, we compared unmodified and sialylated Phl-p5a-peptides in an experimental grass pollen subcutaneous AIT (GP-SCIT) model, 5 to evaluate whether peptide SCIT is effective in suppressing allergic airway inflammation and whether the use of sialylated peptides leads to increased induction of Tregs and enhanced suppression of allergic phenotypes as compared to the unmodified peptide SCIT.…”

Section: Subcutaneous Immunotherapy Using Modified Phl P5a-derived Pementioning

confidence: 99%

Subcutaneous immunotherapy using modified Phl p5a‐derived peptides efficiently alleviates allergic asthma in mice

Hesse

Feenstra

Ambrosini

et al. 2019

Allergy

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Methods for Experimental Allergen Immunotherapy: Subcutaneous and Sublingual Desensitization in Mouse Models of Allergic Asthma

Hesse

Petersen

Nawijn

2020

Methods in Molecular Biology

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

Cited by 16 publications

References 46 publications

1,25(OH)2VitD3 supplementation enhances suppression of grass pollen-induced allergic asthma by subcutaneous and sublingual immunotherapy in a mouse model

1,25(OH)2VitD3 supplementation enhances suppression of grass pollen-induced allergic asthma by subcutaneous and sublingual immunotherapy in a mouse model

Subcutaneous immunotherapy using modified Phl p5a‐derived peptides efficiently alleviates allergic asthma in mice

Methods for Experimental Allergen Immunotherapy: Subcutaneous and Sublingual Desensitization in Mouse Models of Allergic Asthma

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