Peanut-induced intestinal allergy is mediated through a mast cell–IgE–FcεRI–IL-13 pathway

Wang, Meiqin; Takeda, Katsuyuki; Shiraishi, Yuichi; Okamoto, Masakazu; Dakhama, Azzeddine; Joetham, Anthony; Gelfand, Erwin W.

doi:10.1016/j.jaci.2010.05.017

Cited by 67 publications

(63 citation statements)

References 49 publications

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“…The gastrointestinal tract mucus layer is the front line of innate host defense [36] . The accumulation of mucussecreting goblet cells among the gut epithelium in tropomyosin-sensitized mice is similar to that reported in other animal models of food allergies [37,38] . To determine if the elevated percentage of goblet cells over intestinal epithelial cells was associated with increased cell proliferation, we conducted BrdU tracing analysis to examine crypt cell proliferation [25] .…”

Section: Discussionsupporting

confidence: 87%

“…Consistent with other animal models with allergic diarrhea [48,49] , our findings confirm the important role of Th2 cytokines in food allergy. Furthermore, these results are consistent with the higher level of Th2 cytokines, IL-4 and IL-6, and unaltered or lower levels of the Th1 cytokine, IFN-γ, in the intestinal mucosa of patients and mice with food allergy [11,38,50,51] . In light of our previous observation of IL-17 in this animal model and the significance of altered Th17 responses in food allergy [19,52] , future studies should be directed toward examining the contribution and interplay of Th1/Th2 as well as Th17 response in food allergies.…”

Section: Discussionsupporting

confidence: 83%

“…On the other hand, repeated oral gavage and systemic priming are required to trigger the onset of allergic diarrhea in other sensitized mice models of food allergy [20,30,38,47] . Although proven to be antigen specific, allergic diarrhea induced by repeated oral challenge is regarded as unnatural.…”

Section: Discussionmentioning

confidence: 99%

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Gastrointestinal Immune Response to the Shrimp Allergen Tropomyosin: Histological and Immunological Analysis in an Animal Model of Shrimp Tropomyosin Hypersensitivity

Lam¹,

Tong²,

Kwan³

et al. 2015

Int Arch Allergy Immunol

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Background: Shellfish hypersensitivity is among the most common food allergies. A murine model of IgE-mediated shrimp allergy has been established in our laboratory. The aim of this study is to determine the intestinal histological changes and cytokine expression profile of this model sensitized with the major shellfish allergen tropomyosin. Methods: Female Balb/c mice orally sensitized and challenged with recombinant tropomyosin were sacrificed. Continuous sections of duodenum, jejunum and ileum were prepared using the Swiss roll technique for histological and immunological analysis. Duodenal epithelial cell apoptosis and migration were examined. mRNA expression of IL-4, IL-6, IL-10, IL-13, IL-18 and IFN-γ in intestinal tissue was measured via RT-PCR. Results: In tropomyosin-sensitized and challenged mice, an increased number of eosinophils, mast cells and goblet cells was found 24 h after challenge. There were also increased mast cell and goblet cell numbers at 72 h after challenge, but the level of eosinophils decreased. Differences compared with control mice are most prominent at the duodenum compared to the distal regions. In addition, TUNEL assay indicates a significantly higher apoptosis rate in sensitized mice sacrificed 72 h after challenge, and mRNA expression showed a biased Th2/Th1 cytokine profile and a higher level of murine mast cell protease 1. Conclusions: This study documented a multitude of histological and immunological changes in the gut in a murine model of shrimp allergy. Even without repetitive intragastric challenge, shrimp tropomyosin induces an increase in the number of inflammatory cells to varying degrees within the small intestine. This model provides an important tool for testing new therapeutic interventions.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 83%

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Gastrointestinal Immune Response to the Shrimp Allergen Tropomyosin: Histological and Immunological Analysis in an Animal Model of Shrimp Tropomyosin Hypersensitivity

Lam¹,

Tong²,

Kwan³

et al. 2015

Int Arch Allergy Immunol

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“…Eosinophilic inflammation accounts for tissue remodeling by deposition of extracellular matrix proteins, and is associated with subepithelial fibrosis, which leads to gastrointestinal dysfunction [42]. In line with this, eosinophils have been reported to be crucial for the development of food-induced intestinal anaphylaxis [20,22] and several gastrointestinal disorders that cause diarrhea [42,43]. The increased number of mucosal eosinophils observed following intragastric hazelnut challenge, as encountered here, is consistent with these earlier observations, and the pathological relevance of these cells is further highlighted by the significant correlation between the number of eosinophils and the symptom score.…”

mentioning

confidence: 88%

“…Moreover, we measured a slight, yet significant drop in systemic temperature after allergen challenge, which was paralleled by increased hazelnut-specific IgG1, systemic mMCP-1 levels, and mucosal eosinophilia. Therefore, this model reflected not only a local, but also a systemic allergic hypersensitivity and was comparable to other food-induced systemic anaphylaxis models [20,22,23].To analyze the humoral immune response pattern in more detail, we determined the IgE recognition profiles against hazelnut proteins from hazelnut-sensitized mice. In parallel, the IgEbinding profiles of sera from hazelnut-allergic patients were determined.…”

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confidence: 91%

Bortezomib treatment diminishes hazelnut‐induced intestinal anaphylaxis in mice

et al. 2016

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Food allergy is a common health problem and can cause anaphylaxis. Avoidance of the offending food allergen is still the mainstay therapeutic approach. In this study, we investigated the role of plasma cell reduction by proteasome inhibition in a murine model of food allergy and examined the impact of this treatment on the systemic and local immune response. For this purpose, intestinal anaphylaxis was induced in BALB/c mice with the food allergen hazelnut, in conjunction with different adjuvants (alum and Staphylococcal enterotoxin B SEB) and different administration routes (oral and intraperitoneal). In both models, allergy symptoms were observed, but the clinical severity was more pronounced in the hazelnut-alum model than in the hazelnut-SEB model. Accordingly, allergen-specific immunoglobulin E (IgE) against hazelnut was detectable, and mast cell protease-1 in serum was increased after allergen provocation. Treatment with the proteasome inhibitor bortezomib reduced plasma cells and resulted in an abolishment of hazelnut allergen-specific IgE, which was associated with amelioration of clinical symptoms as well as a significant decrease in both CD19 + and follicular B lymphocytes. Our data demonstrate the importance of allergen-specific IgE in food allergy and point to B cells as potential therapeutic targets for its treatment. Keywords: Anaphylaxis B cells Food allergy Immunoglobulin E Proteasome inhibitionAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionAllergic reactions to food are common, and in most cases are caused by type 1-mediated hypersensitivity reactions [1]. Severe cases of food allergy may result in anaphylaxis, which can be fatal [1,2]. Features of food allergy include sensitization paramCorrespondence: Univ. Prof. Dr. med. Margitta Worm e-mail: margitta.worm@charite.de eters, such as the presence of allergen-specific immunoglobulin E (IgE), and typical clinical symptoms. These frequently consist of skin symptoms, such as urticaria and/or angioedema, but also include variable systemic responses, such as respiratory and cardiovascular symptoms [1][2][3]. Until now, the primary therapeutic approach for patients with food allergy has been strict avoidance of the offending food allergen [1]. Hazelnut (Corylus avellana) is a common cause of food allergy in Europe [4][5][6][7], and affects 0.1-0.5% of the population [8]. Hazelnut-allergic Eur. J. Immunol. 2016. 46: 1727-1736 a risk of severe or even fatal reactions [4][5][6]. Although sublingual immunotherapy and/or oral tolerance-induction has recently been shown to be effective for the treatment of peanut-allergic patients [9,10], their use in clinical practice is limited and currently restricted to specialized centers because of the risk of severe side effects. Another therapeutic approach to treat food allergy is the depletion of IgE. Indeed, the efficacy of an anti-IgE treatment has been demonstrated in patients suffering from food allergy [11]. Likewise, the anti-Ig...

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Experimental Approaches to the Study of Food Allergy

Berin

Masilamani

2013

Food Allergy

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Peanut-induced intestinal allergy is mediated through a mast cell–IgE–FcεRI–IL-13 pathway

Abstract: BACKGROUND-Although implicated in the disease, the specific contributions of FcεRI and IL-13 to the pathogenesis of peanut-induced intestinal allergy are not well defined.

Cited by 67 publications

References 49 publications

Gastrointestinal Immune Response to the Shrimp Allergen Tropomyosin: Histological and Immunological Analysis in an Animal Model of Shrimp Tropomyosin Hypersensitivity

Gastrointestinal Immune Response to the Shrimp Allergen Tropomyosin: Histological and Immunological Analysis in an Animal Model of Shrimp Tropomyosin Hypersensitivity

Bortezomib treatment diminishes hazelnut‐induced intestinal anaphylaxis in mice

Experimental Approaches to the Study of Food Allergy

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