title: Epidermal cells enhance interleukin 4 and immunoglobulin E production after stimulation with protein allergen.
abstract: Exposure to certain allergens via epithelial tissues is the primary route for the induction of immunoglobulin E-dependent allergies of the immediate type associated with atopic diseases. In order to address the question whether and how epithelial cells might contribute to the induction or increase of TH2-dependent IgE production, we performed co-culture experiments of syngeneic epidermal cells and cells from the associated lymphoid tissue or spleen (responder cells) of BALB/c mice primed with ovalbumin in vivo. In the presence of ovalbumin in vitro, immunoglobulin E but not immunoglobulin G2a production was significantly enhanced by the addition of epidermal cells, and separation of epidermal cells from responder cells by a membrane that prevented cellular contacts or addition of antibodies against intercellular adhesion molecule-1 reduced the enhancement of immunoglobulin E production induced by epidermal cells. Depletion of major histocompatibility complex class II+ antigen presenting Langerhans cells from the epidermal cells prior to co-culture also reduced the enhancement of immunoglobulin E production induced by epidermal cells. The enhanced immunoglobulin E production was dependent on the induction of TH2 cell-derived interleukin-4 detected in co-cultures because it was completely inhibited after addition of anti-interleukin-4 antibodies that also lead to increased immunoglobulin G2a production. Whereas interleukin-4 was not produced by epidermal cells, interleukin-10 seemed to be one important mediator contributed by epidermal cells. Interleukin-10 skewed the response toward a TH2-mediated IgE response because antibodies against interleukin-10 inhibited interleukin-4 and immunoglobulin E production, whereas they enhanced interferon-gamma and immunoglobulin G2a production.
authors.affiliation: Department of Dermatology, University of Mainz, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Bellinghausen
authors.forename: A H
authors.initials: AH
authors.lastname: Enk
authors.forename: M
authors.initials: M
authors.lastname: Mohamadzadeh
authors.forename: S
authors.initials: S
authors.lastname: Lohmann
authors.forename: J
authors.initials: J
authors.lastname: Knop
authors.forename: J
authors.initials: J
authors.lastname: Saloga
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D003713:Dendritic Cells / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007114:Immunization; D007073:Immunoglobulin E / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000502:physiology; D015603:Keratinocytes / Q000502:physiology; D007801:Langerhans Cells / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D000485:Allergens; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin