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Published in: Clinical and Translational Allergy 1/2012

Open Access 01-12-2012 | Research

Intact skin and not stripped skin is crucial for the safety and efficacy of peanut epicutaneous immunotherapy (EPIT) in mice

Authors: Lucie Mondoulet, Vincent Dioszeghy, Emilie Puteaux, Mélanie Ligouis, Véronique Dhelft, Franck Letourneur, Christophe Dupont, Pierre-Henri Benhamou

Published in: Clinical and Translational Allergy | Issue 1/2012

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Abstract

Background

Epicutaneous immunotherapy (EPIT) on intact skin with an epicutaneous delivery system has already been used in preclinical and clinical studies. In epicutaneous vaccination and immunotherapy, the stripping of skin before application of the allergen is suggested to facilitate the passage of allergen through immune cells.

Objectives

The aim of this study was to compare the immunological response induced by EPIT performed on intact and stripped skin in a mouse model of peanut allergy.

Methods

After oral sensitization with peanut and cholera toxin, BALB/c mice were epicutaneously treated using an epicutaneous delivery system (Viaskin® (DBV Technologies, Paris) applied either on intact skin or on stripped skin. Following EPIT, mice received an exclusive oral peanut regimen, aimed at triggering esophageal and jejunal lesions. We assessed eosinophil infiltration by histology, mRNA expression in the esophagus, antibody levels and peripheral T-cell response.

Results

EPIT on intact skin significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines) as well as esophageal eosinophilia (2.7 ± 0.9, compared to Sham 19.9 ± 1.5, p < 0.01), mRNA expression of Th2 cytokines in tissue and intestinal villus sub-atrophia (2.9 ± 0.2 vs Sham, 2.1 ± 0.2, p < 0.05). By contrast, EPIT on stripped skin reinforced Th2 systemic immunological response as well as eosinophil infiltration (26.8 ± 15.1), mRNA expression of Th2 cytokines and duodenal villus/crypt-ratio (2.4 ± 0.3).

Conclusions

Epicutaneous allergen-specific immunotherapy needs the integrity of superficial layers of the stratum corneum to warranty safety of treatment and to induce a tolerogenic profile of the immune response.
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Literature
1.
go back to reference Dupont C, Kalach N, Soulaines P, Legoue-Morillon S, Piloquet H, Benhamou PH: Cow’s milk epicutaneous immunotherapy in children: a pilot trial of safety, acceptability, and impact on allergic reactivity. J Allergy Clin Immunol. 2010, 125: 1165-1167. 10.1016/j.jaci.2010.02.029.CrossRefPubMed Dupont C, Kalach N, Soulaines P, Legoue-Morillon S, Piloquet H, Benhamou PH: Cow’s milk epicutaneous immunotherapy in children: a pilot trial of safety, acceptability, and impact on allergic reactivity. J Allergy Clin Immunol. 2010, 125: 1165-1167. 10.1016/j.jaci.2010.02.029.CrossRefPubMed
2.
go back to reference Dioszeghy V, Mondoulet L, Dhelft V, Ligouis M, Puteaux E, Benhamou PH, Dupont C: Epicutaneous Immunotherapy Results in Rapid Allergen Uptake by Dendritic Cells through Intact Skin and Downregulates the Allergen-Specific Response in Sensitized Mice. J Immunol. 2011, 186: 5629-5637. 10.4049/jimmunol.1003134.CrossRefPubMed Dioszeghy V, Mondoulet L, Dhelft V, Ligouis M, Puteaux E, Benhamou PH, Dupont C: Epicutaneous Immunotherapy Results in Rapid Allergen Uptake by Dendritic Cells through Intact Skin and Downregulates the Allergen-Specific Response in Sensitized Mice. J Immunol. 2011, 186: 5629-5637. 10.4049/jimmunol.1003134.CrossRefPubMed
3.
go back to reference Mondoulet L, Dioszeghy V, Ligouis M, Dhelft V, Dupont C, Benhamou PH: Epicutaneous immunotherapy on intact skin using a new delivery system in a murine model of allergy. Clin Exp Allergy. 2010, 40: 659-667.CrossRefPubMed Mondoulet L, Dioszeghy V, Ligouis M, Dhelft V, Dupont C, Benhamou PH: Epicutaneous immunotherapy on intact skin using a new delivery system in a murine model of allergy. Clin Exp Allergy. 2010, 40: 659-667.CrossRefPubMed
4.
go back to reference Mondoulet L, Dioszeghy V, Vanoirbeek J, Nemery B, Dupont C, Benhamou PH: Epicutaneous immunotherapy using a new epicutaneous delivery system in mice sensitized to peanut. Int Arch Allergy Immunol. 2011, 154: 299-309. 10.1159/000321822.CrossRefPubMed Mondoulet L, Dioszeghy V, Vanoirbeek J, Nemery B, Dupont C, Benhamou PH: Epicutaneous immunotherapy using a new epicutaneous delivery system in mice sensitized to peanut. Int Arch Allergy Immunol. 2011, 154: 299-309. 10.1159/000321822.CrossRefPubMed
5.
go back to reference Mondoulet L, Dioszeghy V, Larcher T, Ligouis M, Dhelft V, Puteaux E, Cherel Y, Letourneur F, Dupont C, Benhamou PH: Epicutaneous Immunotherapy (EPIT) Blocks the Allergic Esophago-Gastro-Enteropathy Induced by Sustained Oral Exposure to Peanuts in Sensitized Mice. PLoS One. 2012, 7: e31967-10.1371/journal.pone.0031967.PubMedCentralCrossRefPubMed Mondoulet L, Dioszeghy V, Larcher T, Ligouis M, Dhelft V, Puteaux E, Cherel Y, Letourneur F, Dupont C, Benhamou PH: Epicutaneous Immunotherapy (EPIT) Blocks the Allergic Esophago-Gastro-Enteropathy Induced by Sustained Oral Exposure to Peanuts in Sensitized Mice. PLoS One. 2012, 7: e31967-10.1371/journal.pone.0031967.PubMedCentralCrossRefPubMed
6.
go back to reference Glenn GM, Scharton-Kersten T, Vassell R, Mallett CP, Hale TL, Alving CR: Transcutaneous immunization with cholera toxin protects mice against lethal mucosal toxin challenge. J Immunol. 1998, 161: 3211-3214.PubMed Glenn GM, Scharton-Kersten T, Vassell R, Mallett CP, Hale TL, Alving CR: Transcutaneous immunization with cholera toxin protects mice against lethal mucosal toxin challenge. J Immunol. 1998, 161: 3211-3214.PubMed
7.
go back to reference Glenn GM, Rao M, Matyas GR, Alving CR: Skin immunization made possible by cholera toxin. Nature. 1998, 391: 851-10.1038/36014.CrossRefPubMed Glenn GM, Rao M, Matyas GR, Alving CR: Skin immunization made possible by cholera toxin. Nature. 1998, 391: 851-10.1038/36014.CrossRefPubMed
8.
go back to reference Senti G, Graf N, Haug S, Ruedi N, Von MS, Sonderegger T, Johansen P, Kundig TM: Epicutaneous allergen administration as a novel method of allergen-specific immunotherapy. J Allergy Clin Immunol. 2009, 124: 997-1002. 10.1016/j.jaci.2009.07.019.CrossRefPubMed Senti G, Graf N, Haug S, Ruedi N, Von MS, Sonderegger T, Johansen P, Kundig TM: Epicutaneous allergen administration as a novel method of allergen-specific immunotherapy. J Allergy Clin Immunol. 2009, 124: 997-1002. 10.1016/j.jaci.2009.07.019.CrossRefPubMed
9.
go back to reference Li XM, Serebrisky D, Lee SY, Huang CK, Bardina L, Schofield BH, Stanley JS, Burks AW, Bannon GA, Sampson HA: A murine model of peanut anaphylaxis: T- and B-cell responses to a major peanut allergen mimic human responses. J Allergy Clin Immunol. 2000, 106: 150-158. 10.1067/mai.2000.107395.CrossRefPubMed Li XM, Serebrisky D, Lee SY, Huang CK, Bardina L, Schofield BH, Stanley JS, Burks AW, Bannon GA, Sampson HA: A murine model of peanut anaphylaxis: T- and B-cell responses to a major peanut allergen mimic human responses. J Allergy Clin Immunol. 2000, 106: 150-158. 10.1067/mai.2000.107395.CrossRefPubMed
10.
go back to reference Strid J, Thomson M, Hourihane J, Kimber I, Strobel S: A novel model of sensitization and oral tolerance to peanut protein. Immunology. 2004, 113: 293-303. 10.1111/j.1365-2567.2004.01989.x.PubMedCentralCrossRefPubMed Strid J, Thomson M, Hourihane J, Kimber I, Strobel S: A novel model of sensitization and oral tolerance to peanut protein. Immunology. 2004, 113: 293-303. 10.1111/j.1365-2567.2004.01989.x.PubMedCentralCrossRefPubMed
11.
go back to reference Strid J, Hourihane J, Kimber I, Callard R, Strobel S: Epicutaneous exposure to peanut protein prevents oral tolerance and enhances allergic sensitization. Clin Exp Allergy. 2005, 35: 757-766. 10.1111/j.1365-2222.2005.02260.x.CrossRefPubMed Strid J, Hourihane J, Kimber I, Callard R, Strobel S: Epicutaneous exposure to peanut protein prevents oral tolerance and enhances allergic sensitization. Clin Exp Allergy. 2005, 35: 757-766. 10.1111/j.1365-2222.2005.02260.x.CrossRefPubMed
12.
go back to reference Strid J, Callard R, Strobel S: Epicutaneous immunization converts subsequent and established antigen-specific T helper type 1 (Th1) to Th2-type responses. Immunology. 2006, 119: 27-35. 10.1111/j.1365-2567.2006.02401.x.PubMedCentralCrossRefPubMed Strid J, Callard R, Strobel S: Epicutaneous immunization converts subsequent and established antigen-specific T helper type 1 (Th1) to Th2-type responses. Immunology. 2006, 119: 27-35. 10.1111/j.1365-2567.2006.02401.x.PubMedCentralCrossRefPubMed
13.
go back to reference Spergel JM, Mizoguchi E, Brewer JP, Martin TR, Bhan AK, Geha RS: Epicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methacholine after single exposure to aerosolized antigen in mice. J Clin Invest. 1998, 101: 1614-1622. 10.1172/JCI1647.PubMedCentralCrossRefPubMed Spergel JM, Mizoguchi E, Brewer JP, Martin TR, Bhan AK, Geha RS: Epicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methacholine after single exposure to aerosolized antigen in mice. J Clin Invest. 1998, 101: 1614-1622. 10.1172/JCI1647.PubMedCentralCrossRefPubMed
14.
go back to reference Vaali K, Puumalainen TJ, Lehto M, Wolff H, Rita H, Alenius H, Palosuo T: Murine model of food allergy after epicutaneous sensitization: role of mucosal mast cell protease-1. Scand J Gastroenterol. 2006, 41: 1405-1413. 10.1080/00365520600815639.CrossRefPubMed Vaali K, Puumalainen TJ, Lehto M, Wolff H, Rita H, Alenius H, Palosuo T: Murine model of food allergy after epicutaneous sensitization: role of mucosal mast cell protease-1. Scand J Gastroenterol. 2006, 41: 1405-1413. 10.1080/00365520600815639.CrossRefPubMed
15.
go back to reference Kenney RT, Yu J, Guebre-Xabier M, Frech SA, Lambert A, Heller BA, Ellingsworth LR, Eyles JE, Williamson ED, Glenn GM: Induction of protective immunity against lethal anthrax challenge with a patch. J Infect Dis. 2004, 190: 774-782. 10.1086/422694.CrossRefPubMed Kenney RT, Yu J, Guebre-Xabier M, Frech SA, Lambert A, Heller BA, Ellingsworth LR, Eyles JE, Williamson ED, Glenn GM: Induction of protective immunity against lethal anthrax challenge with a patch. J Infect Dis. 2004, 190: 774-782. 10.1086/422694.CrossRefPubMed
16.
go back to reference Lack G, Fox D, Northstone K, Golding J: Factors associated with the development of peanut allergy in childhood. N Engl J Med. 2003, 348: 977-985. 10.1056/NEJMoa013536.CrossRefPubMed Lack G, Fox D, Northstone K, Golding J: Factors associated with the development of peanut allergy in childhood. N Engl J Med. 2003, 348: 977-985. 10.1056/NEJMoa013536.CrossRefPubMed
17.
go back to reference Fox AT, Sasieni P, Du TG, Syed H, Lack G: Household peanut consumption as a risk factor for the development of peanut allergy. J Allergy Clin Immunol. 2009, 123: 417-423. 10.1016/j.jaci.2008.12.014.CrossRefPubMed Fox AT, Sasieni P, Du TG, Syed H, Lack G: Household peanut consumption as a risk factor for the development of peanut allergy. J Allergy Clin Immunol. 2009, 123: 417-423. 10.1016/j.jaci.2008.12.014.CrossRefPubMed
19.
go back to reference Senti G, von Moos S, Tay F, Graf N, Sonderegger T, Johansen P, Kundig TM: Epicutaneous allergen-specific immunotherapy ameliorates grass pollen-induced rhinoconjunctivitis: A double-blind, placebo-controlled dose escalation study. J Allergy Clin Immunol. 2012, 129: 128-135. 10.1016/j.jaci.2011.08.036.CrossRefPubMed Senti G, von Moos S, Tay F, Graf N, Sonderegger T, Johansen P, Kundig TM: Epicutaneous allergen-specific immunotherapy ameliorates grass pollen-induced rhinoconjunctivitis: A double-blind, placebo-controlled dose escalation study. J Allergy Clin Immunol. 2012, 129: 128-135. 10.1016/j.jaci.2011.08.036.CrossRefPubMed
20.
go back to reference Dioszeghy V, Mondoulet L, Dhelft V, Ligouis M, Puteaux E, Dupont C, Benhamou PH: Epicutaneous immunotherapy requires intact skin and not stripped skin to properly activate and mature dendritic cells toward induction of desensitization (EAACI Congress, PS 1326). Allergy. 2011, 66 (s94): 482-642. Dioszeghy V, Mondoulet L, Dhelft V, Ligouis M, Puteaux E, Dupont C, Benhamou PH: Epicutaneous immunotherapy requires intact skin and not stripped skin to properly activate and mature dendritic cells toward induction of desensitization (EAACI Congress, PS 1326). Allergy. 2011, 66 (s94): 482-642.
21.
go back to reference Kalach N, Soulaines P, De BD, Dupont C: A pilot study of the usefulness and safety of a ready-to-use atopy patch test (Diallertest) versus a comparator (Finn Chamber) during cow’s milk allergy in children. J Allergy Clin Immunol. 2005, 116: 1321-1326. 10.1016/j.jaci.2005.08.033.CrossRefPubMed Kalach N, Soulaines P, De BD, Dupont C: A pilot study of the usefulness and safety of a ready-to-use atopy patch test (Diallertest) versus a comparator (Finn Chamber) during cow’s milk allergy in children. J Allergy Clin Immunol. 2005, 116: 1321-1326. 10.1016/j.jaci.2005.08.033.CrossRefPubMed
22.
go back to reference He R, Oyoshi MK, Garibyan L, Kumar L, Ziegler SF, Geha RS: TSLP acts on infiltrating effector T cells to drive allergic skin inflammation. Proc Natl Acad Sci USA. 2008, 105: 11875-11880. 10.1073/pnas.0801532105.PubMedCentralCrossRefPubMed He R, Oyoshi MK, Garibyan L, Kumar L, Ziegler SF, Geha RS: TSLP acts on infiltrating effector T cells to drive allergic skin inflammation. Proc Natl Acad Sci USA. 2008, 105: 11875-11880. 10.1073/pnas.0801532105.PubMedCentralCrossRefPubMed
23.
go back to reference Oyoshi MK, Larson RP, Ziegler SF, Geha RS: Mechanical injury polarizes skin dendritic cells to elicit a T(H)2 response by inducing cutaneous thymic stromal lymphopoietin expression. J Allergy Clin Immunol. 2010, 126: 976-984. 10.1016/j.jaci.2010.08.041.PubMedCentralCrossRefPubMed Oyoshi MK, Larson RP, Ziegler SF, Geha RS: Mechanical injury polarizes skin dendritic cells to elicit a T(H)2 response by inducing cutaneous thymic stromal lymphopoietin expression. J Allergy Clin Immunol. 2010, 126: 976-984. 10.1016/j.jaci.2010.08.041.PubMedCentralCrossRefPubMed
24.
go back to reference Li M, Hener P, Zhang Z, Kato S, Metzger D, Chambon P: Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis. Proc Natl Acad Sci USA. 2006, 103: 11736-11741. 10.1073/pnas.0604575103.PubMedCentralCrossRefPubMed Li M, Hener P, Zhang Z, Kato S, Metzger D, Chambon P: Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis. Proc Natl Acad Sci USA. 2006, 103: 11736-11741. 10.1073/pnas.0604575103.PubMedCentralCrossRefPubMed
25.
go back to reference Li W, Zhang Z, Saxon A, Zhang K: Prevention of oral food allergy sensitization via skin application of food allergen in a mouse model. Allergy. 2012, 67: 622-629. 10.1111/j.1398-9995.2012.02798.x.CrossRefPubMed Li W, Zhang Z, Saxon A, Zhang K: Prevention of oral food allergy sensitization via skin application of food allergen in a mouse model. Allergy. 2012, 67: 622-629. 10.1111/j.1398-9995.2012.02798.x.CrossRefPubMed
26.
go back to reference de Gomez AM, Vocanson M, Hacini-Rachinel F, Taillardet M, Sparwasser T, Kissenpfennig A, Malissen B, Kaiserlian D, Dubois B: Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8(+) T cells and activating Foxp3(+) regulatory T cells. J Clin Invest. 2012, 122: 1700-1711. 10.1172/JCI59725.CrossRef de Gomez AM, Vocanson M, Hacini-Rachinel F, Taillardet M, Sparwasser T, Kissenpfennig A, Malissen B, Kaiserlian D, Dubois B: Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8(+) T cells and activating Foxp3(+) regulatory T cells. J Clin Invest. 2012, 122: 1700-1711. 10.1172/JCI59725.CrossRef
Metadata
Title
Intact skin and not stripped skin is crucial for the safety and efficacy of peanut epicutaneous immunotherapy (EPIT) in mice
Authors
Lucie Mondoulet
Vincent Dioszeghy
Emilie Puteaux
Mélanie Ligouis
Véronique Dhelft
Franck Letourneur
Christophe Dupont
Pierre-Henri Benhamou
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Clinical and Translational Allergy / Issue 1/2012
Electronic ISSN: 2045-7022
DOI
https://doi.org/10.1186/2045-7022-2-22

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