title: Epicutaneous immunization with ovalbumin and CpG induces TH1/TH17 cytokines, which regulate IgE and IgG2a production.
abstract: Subcutaneous allergen-specific immunotherapy is a standard route for the immunotherapy of allergic diseases. It modulates the course of allergy and can generate long-term remission. However, subcutaneous allergen-specific immunotherapy can also induce anaphylaxis in some patients, and therefore additional routes of administration should be investigated to improve the safety and tolerability of immunotherapy.
  
  
  
  We sought to determine whether epicutaneous treatment with antigen in the presence of a Toll-like receptor 9 agonist can suppress TH2-mediated responses in an antigen-specific manner.
  
  
  
  Epicutaneous immunization was performed by applying a skin patch soaked with ovalbumin (OVA) plus CpG, and its suppressor activity was determined by using the mouse model of atopic dermatitis. Finally, adoptive cell transfers were implemented to characterize the regulatory cells that are induced by epicutaneous immunization.
  
  
  
  Epicutaneous immunization with OVA and CpG reduces the production of OVA-specific IgE and increases the synthesis of OVA-specific IgG2a antibodies in an antigen-specific manner. Moreover, eosinophil peroxidase activity in the skin and production of IL-4, IL-5, IL-10, and IL-13 are suppressed. The observed reduction of IgE synthesis is transferable with T-cell receptor (TCR) αβ(+)CD4(+)CD25(-) cells, whereas IgG2a production is dependent on both TCRαβ(+) and TCRγδ(+) T cells. Further experiments show that the described phenomenon is myeloid differentiation primary response 88, IFN-γ, and IL-17A dependent. Finally, the results suggest that epicutaneous immunization with OVA and CpG decreases the synthesis of OVA-specific IgE and skin eosinophil peroxidase activity in mice with ongoing skin allergy.
  
  
  
  Epicutaneous application of protein antigen in the presence of adjuvant could be an attractive needle-free and self-administered immunotherapy for allergic diseases.
authors.affiliation: Department of Medical Biology, Health Science Faculty, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Majewska-Szczepanik
authors.affiliation: Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Conn.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Askenase
authors.affiliation: Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Conn.
authors.forename: Francis M
authors.initials: FM
authors.lastname: Lobo
authors.affiliation: Department of Medical Biology, Health Science Faculty, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Marcińska
authors.affiliation: Department of Internal Medicine, Section of Endocrinology, Yale University School of Medicine, New Haven, Conn.
authors.forename: Li
authors.initials: L
authors.lastname: Wen
authors.affiliation: Department of Medical Biology, Health Science Faculty, Jagiellonian University Medical College, Krakow, Poland. Electronic address: mmszczep@cyf-kr.edu.pl.
authors.forename: Marian
authors.initials: M
authors.lastname: Szczepanik
mesh_terms: D016207:Cytokines / Q000096:biosynthesis*; D007114:Immunization; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000378:metabolism
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D008024:Ligands; D053594:Myeloid Differentiation Factor 88; D009838:Oligodeoxyribonucleotides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D051217:Toll-Like Receptor 9; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: Epicutaneous immunization; IgE; IgG(2a); T(H)1; T(H)17; Toll-like receptor 9; atopic dermatitis; eosinophil peroxidase
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