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Cited by 58Allergic Rhinitis and SensitizationAdvanced Drug Delivery SystemsFood Allergy and Anaphylaxis Research

M cell targeting with Aleuria aurantia lectin as a novel approach for oral allergen immunotherapy

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Roth-Walter, Franziska, Schöll, Isabella, Untersmayr, Eva, Fuchs, Renate, Boltz-Nitulescu, George, Weissenböck, Andrea, Scheiner, Otto, Gabor, Franz +1 more·2004·Journal of Allergy and Clinical Immunology
DOI 10.1016/j.jaci.2004.08.010
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Abstract

Background The extent and quality of the immune response to orally applied allergens may critically depend on the precise site of uptake at the intestinal mucosa.Objective The aim of this study was to construct allergen vehicles optimized for oral allergen immunotherapy.Methods By using a murine model, we examined the immunomodulatory effect of birch pollen proteins entrapped in poly(D,L-lactide-co-glycolide) microspheres, which were specifically targeted to enterocytes or to M cells, in an ongoing T h 2 response. BALB/c mice express different carbohydrates on these 2 cell types. To target the sialylic residues on murine enterocytes, we functionalized microspheres with wheat germ agglutinin (WGA) and, to target alpha-L-fucose on M cells, with a lectin from Aleuria aurantia (AAL), the orange peel mushroom.Results Both WGA and AAL functionalization enhanced binding to human Caco2 cells substantially, which express sialylic and, as carcinoma cells, also alpha-L-fucose residues. Different groups of BALB/c mice were first sensitized to birch pollen and subsequently fed with birch pollen-loaded functionalized (WGA microspheres, AAL microspheres) or nonfunctionalized, birch pollen extract-loaded particles. When mice were fed with AAL microspheres, birch pollen-specific IgG2a, but not IgG1 or IgE, increased significantly. As expected, in a 3 H-thymidin assay, their splenocytes proliferated specifically on birch pollen stimulation. Both targeting strategies, using WGA or AAL, induced IL-10 as well as IL-4 production. However, in AAL microsphere-treated mice, IFN-gamma synthesis was significantly increased, which may be responsible for the significant IgG2a production in this group.Conclusion Our data indicate that targeting M cells by using AAL-coated allergen vehicles may be a promising strategy for oral allergen immunotherapy.

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  • AAL-functionalized MPs are a potential novel strategy for oral immunotherapy against Th2-biased diseases like allergy.

    “These studies corroborate the potential of AAL functionalized MPs as a novel strategy for oral immunotherapy against Th2-biased diseases, such as allergy.”

    From Use of lectin-functionalized particles for oral immunotherapy (2012) · cites this paper as [75]

  • In birch pollen-sensitized mice, 15 oral treatments with AAL-functionalized allergen-loaded microspheres increased birch pollen-specific IgG2a without affecting IgE and IgG1, indicating Th1-biased immune response.

    “Animals fed with AAL-functionalized, allergen-loaded microspheres for 15-times revealed an increase of birch pollen-specific IgG2a, whereas IgE and IgG1 were not affected, indicating the induction of a prominent Th1-biased immune response.”

    From Use of lectin-functionalized particles for oral immunotherapy (2012) · cites this paper as [75]

  • Spleen cells from animals treated orally with AAL MPs secreted significantly more IL-10 and IFN-γ.

    “spleen cells of animals being treated with AAL MPs via the oral route secreted significantly more T-regulatory cytokine IL-10 and Th1 cytokine IFN-γ [75].”

    From Use of lectin-functionalized particles for oral immunotherapy (2012) · cites this paper as [75]

  • Lectins binding to the M-cell glycocalyx may serve as specific targeters on carrier systems for antigen or drug delivery to the immune system.

    “lectins binding to the M-cell glycocalyx may serve as specific targeters on carrier systems for antigen or drug delivery to the immune system [9,13–15].”

    From Characterization of Vibrio cholerae neuraminidase as an immunomodulator for novel formulation of oral allergy immunotherapy (2018) · cites this paper as [13]

  • Oral application of allergen-loaded, AAL-coated PLGA-MPs to birch pollen-sensitized mice beneficially modulated an established Th2-biased immune response.

    “Moreover, oral application of allergen-loaded, AAL-coated PLGA-MPs to birch pollen-sensitized mice beneficially modulated an established Th2 biased immune response [13].”

    From Characterization of Vibrio cholerae neuraminidase as an immunomodulator for novel formulation of oral allergy immunotherapy (2018) · cites this paper as [13]

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Research works printed but not linked: 1

  1. Gabor F, Wirth M. Lectin-mediated drug delivery: fundamentals and perspectives. STP Pharma Sci 2003;13:3-16.

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Authors
Roth-Walter, F., Schöll, I., Untersmayr, E., Fuchs, R., Boltz-Nitulescu, G., Weissenböck, A., Scheiner, O., Gabor, F., & Jensen-Jarolim, E.
Affiliations
  • Medical University of Vienna (AT)
  • University of Vienna (AT)
ORCID
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2004-12
Volume
114
Issue
6
Pages
1362-1368
ISSN
0091-6749 (ISSN-L)
DOI
10.1016/j.jaci.2004.08.010
OpenAlex
W1969393348
Cited by
58
References
45
Citations by year
2026: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 1 · 2013: 2 · 2012: 4
FWCI
2.82
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Allergy and Clinical Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Science Foundation
Topics
  • Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
Keywords
M cells, Aleuria aurantia lectin, birch pollen, wheat germ agglutinin, enterocytes, sialic acid, alpha-L-fucose, IgG2a, Th2 immune response, IL-10, interferon-gamma, IL-4, Caco-2 cells, oral mucosa
MeSH terms
Polylactic Acid-Polyglycolic Acid Copolymer, Administration, Oral, Animals, Desensitization, Immunologic, Female, Glycolates, Humans, Immunoglobulin G, Interferon-gamma, Lymphocyte Activation, Mice, Inbred BALB C, Microspheres, Polyglycolic Acid, Caco-2 Cells, Lactic Acid, Enterocytes, Lectins, Mice

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