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Utrecht, Netherlands

Smit J.J.,University Utrecht | Smit J.J.,Utrecht Center for Food Allergy | Bol-Schoenmakers M.,University Utrecht | Hassing I.,University Utrecht | And 4 more authors.
Clinical and Experimental Allergy | Year: 2011

Background Food allergy affects approximately 6% of children and is the leading cause of hospitalization for anaphylactic reactions in westernized countries. Crucial in the establishment of allergy is the activation of dendritic cells (DC) leading to T helper 2-mediated responses. Objective We, therefore, investigated whether changes in DC subsets precede the establishment of food allergy, and which DC subsets have functional relevance during allergic sensitization in a mouse model. Methods Changes in DC populations in the intestine were analysed after exposure to cholera toxin alone and in combination with peanut extract (PE) as an allergen. To study the functional role of DC subsets in relation to food allergy, we used expansion of DC in vivo by treatment with Flt3L. Results Sensitization to PE in this mouse model was accompanied by a shift in DC subsets in intestinal tissues towards more CD11b +DC and less CD103 +DC. No significant changes in the plasmacytoid DC (pDC) numbers were observed. Flt3L treatment, resulting in the expansion of all DC subtypes, inhibited allergic manifestations in our model, including Th2 cytokine production, PE-specific IgE and PE-induced mast cell degranulation. pDC depletion reversed Flt3L-induced inhibition of IgE responses and mast cell degranulation. Conclusions and Clinical Relevance The establishment of food allergy is accompanied by profound changes in DC subsets in the intestine towards more inflammatory CD11b +DC. In addition, expansion of DC numbers by Flt3L, in particular pDC, inhibits the establishment of allergic manifestations in the intestine. These findings are of relevance for understanding the role of DC subsets early during the process of allergic sensitization, and may lead to new therapeutic or prophylactic opportunities to prevent food allergy. © 2011 Blackwell Publishing Ltd.

Schulz V.J.,University Utrecht | Smit J.J.,University Utrecht | Smit J.J.,Utrecht Center for Food Allergy | Willemsen K.J.,University Utrecht | And 7 more authors.
Toxicological Sciences | Year: 2011

Food allergy is an increasing health problem in Western countries. Previously, it has been shown that the intensity of food allergic reactions can be regulated by regulatory T (T reg) cells. In addition, it has been shown that activation of the aryl hydrocarbon receptor (AhR) regulates T-cell responses by induction of T reg cells. Therefore, we hypothesized that activation of the AhR pathway can suppress development of food allergic responses through the induction of T reg cells. This was investigated by using a mouse model for peanut allergy. C3H/HeOuJ mice (AhR b-2) were sensitized to peanut by administering peanut extract (PE) by gavage in the presence of cholera toxin and were treated with the prototypical AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.6, 1.7, 5, and 15 μg/kg body weight) on days 3 and 11 orally. The functional role of CD4 +CD25 +Foxp3 + T reg cells was investigated by depleting these cells with anti-CD25 mAb during sensitization to PE. TCDD treatment dose dependently suppressed sensitization to peanut (PE-specific IgE, IgG1, and IgG2a and PE-induced IL-5, IL-10, and IL-13, respectively). The percentage, but not the number, of CD4 +CD25 +Foxp3 + T reg cells dose dependently increased by AhR activation in both spleen and mesenteric lymph nodes. Depletion of CD4 +CD25 +Foxp3 + T reg cells markedly reversed the suppressive effect of TCDD on PE-specific antibody levels and PE-induced IL-5, IL-10, and IL-13 cytokine production. Present data demonstrate for the first time that activation of the AhR by TCDD suppressed the development of Th2-mediated food allergic responses. A functional shift within the CD4 + cell population toward CD4 +CD25 +Foxp3 + T reg cells appeared to underlie this effect. This suggests that the AhR pathway might provide potential therapeutic targets to treat food allergic diseases. © The Author 2011. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.

Verhoeckx K.C.M.,TNO | Verhoeckx K.C.M.,University Utrecht | Verhoeckx K.C.M.,Utrecht Center for Food Allergy | van Broekhoven S.,Wageningen University | And 12 more authors.
Food and Chemical Toxicology | Year: 2014

Scope: Due to the imminent growth of the world population, shortage of protein sources for human consumption will arise in the near future. Alternative and sustainable protein sources (e.g. insects) are being explored for the production of food and feed. In this project, the safety of Yellow mealworms (Tenebrio molitor L.) for human consumption was tested using approaches as advised by the European Food Safety Authority for allergenicity risk assessment. Methods and results: Different Yellow mealworm protein fractions were prepared, characterised, and tested for cross-reactivity using sera from patients with an inhalation or food allergy to biologically related species (House dust mite (HDM) and crustaceans) by immunoblotting and basophil activation. Furthermore, the stability was investigated using an in vitro pepsin digestion test. IgE from HDM- and crustacean allergic patients cross-reacted with Yellow mealworm proteins. This cross-reactivity was functional, as shown by the induction of basophil activation. The major cross-reactive proteins were identified as tropomyosin and arginine kinase, which are well known allergens in arthropods. These proteins were moderately stable in the pepsin stability test. Conclusion: Based on these cross-reactivity studies, there is a realistic possibility that HDM- and crustacean allergic patients may react to food containing Yellow mealworm proteins. © 2014 Elsevier Ltd.

Broekman H.,Afdeling Dermatologie Allergologie | Broekman H.,Utrecht Center for Food Allergy | Verhoeckx K.,Afdeling Dermatologie Allergologie | Verhoeckx K.,TNO | And 9 more authors.
Nederlands Tijdschrift voor Dermatologie en Venereologie | Year: 2014

Patients with a shrimp allergy, can also react to similar allergens from other crustaceans, shellfish or mollusks. Due to the quest for new protein sources, insects are being looked at to see if they could be a source for these proteins. In vitro studies show that the crustacean allergic patients are at risk to develop allergic symptoms when consuming these proteins, because of the similarity between allergens in shellfish and insects.© 2014 De Nederlandse Vereniging voor Dermatologie en Venereologie.

Bol-Schoenmakers M.,University Utrecht | Marcondes Rezende M.,University Utrecht | Marcondes Rezende M.,Utrecht Center for Food Allergy | Bleumink R.,University Utrecht | And 7 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2011

Background: Food allergy affects approximately 5% of children and is the leading cause of hospitalization for anaphylactic reactions in westernized countries. The mucosal adjuvant cholera toxin induces allergic sensitization to co-administered proteins in mice, while feeding the protein alone induces oral tolerance. Intestinal γδ T cells could be of importance in the induction of oral tolerance. This study aims to investigate whether γδ T cells have functional relevance in food allergic sensitization. Methods: Changes in γδ T cells on days 1, 2, 3, and 7 after initiation of food allergy were evaluated using flowcytometry. Furthermore, the anti-γδ T-cell receptor (TCR) antibody UC7 was used to block the γδ TCR in mice in vivo, followed by sensitization to peanut. After 4 weeks, peanut-specific antibodies in serum and cytokine production in spleen were measured. Results: Induction of food allergy resulted in a profound decrease in the percentage of γδ T cells in intestinal tissues and Peyers Patches, but not in mesenteric lymph nodes or spleen. This decrease could be detected from days 1 to 2 after the initiation of food allergy and the number of γδ T cells returned to normal on day 7. Blockade of the γδ TCR resulted in elevated food allergic responses upon sensitization with peanut characterized by increased IgE and Th2 cytokine production in splenocytes. Conclusion: These results demonstrate a unique regulatory role of γδ T cells, suggesting that targeting γδ T cells in the intestine may contribute to strategies to prevent and possibly treat food allergy. © 2010 John Wiley & Sons A/S.

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