title: Epicutaneous sensitization to house dust mite allergen requires interferon regulatory factor 4-dependent dermal dendritic cells.
abstract: BACKGROUND
  Exposure to allergens, such as house dust mite (HDM), through the skin often precedes allergic inflammation in the lung. It was proposed that TH2 sensitization through the skin occurs when skin barrier function is disrupted by, for example, genetic predisposition, mechanical damage, or the enzymatic activity of allergens.
  
  
  OBJECTIVE
  We sought to study how HDM applied to unmanipulated skin leads to TH2 sensitization and to study which antigen-presenting cells mediate this process.
  
  
  METHODS
  HDM was applied epicutaneously by painting HDM on unmanipulated ear skin or under an occlusive tape. HDM challenge was through the nose. Mouse strains lacking different dendritic cell (DC) populations were used, and 1-DER T cells carrying a transgenic T-cell receptor reactive to Der p 1 allergen were used as a readout for antigen presentation. The TH2-inducing capacity of sorted skin-derived DC subsets was determined by means of adoptive transfer to naive mice.
  
  
  RESULTS
  Epicutaneous HDM application led to TH2 sensitization and eosinophilic airway inflammation upon intranasal HDM challenge. Skin sensitization did not require prior skin damage or enzymatic activity within HDM extract, yet was facilitated by applying the allergen under an occlusive tape. Primary proliferation of 1-DER T cells occurred only in the regional skin-draining lymph nodes. Epicutaneous sensitization was found to be driven by 2 variants of interferon regulatory factor 4-dependent dermal type 2 conventional DC subsets and not by epidermal Langerhans cells.
  
  
  CONCLUSIONS
  These findings identify skin type 2 conventional DCs as crucial players in TH2 sensitization to common inhaled allergens that enter the body through the skin and can provoke features of allergic asthma.
authors.affiliation: VIB Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine, Ghent University, Ghent, Belgium; Receptor Research Laboratories, Nuclear Receptor Lab, VIB Center for Medical Biotechnology, Ghent, Belgium; Department of Biochemistry, Ghent University, Ghent, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Deckers
authors.affiliation: VIB Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Dorine
authors.initials: D
authors.lastname: Sichien
authors.affiliation: VIB Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine, Ghent University, Ghent, Belgium; Department of Pulmonary Medicine, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands.
authors.forename: Maud
authors.initials: M
authors.lastname: Plantinga
authors.affiliation: VIB Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine, Ghent University, Ghent, Belgium.
authors.forename: Justine
authors.initials: J
authors.lastname: Van Moorleghem
authors.affiliation: VIB Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine, Ghent University, Ghent, Belgium.
authors.forename: Manon
authors.initials: M
authors.lastname: Vanheerswynghels
authors.affiliation: VIB Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Esther
authors.initials: E
authors.lastname: Hoste
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Marseille, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.affiliation: INSERM U1011, Institut Pasteur de Lille, Université Lille Nord de France, Lille, France.
authors.forename: David
authors.initials: D
authors.lastname: Dombrowicz
authors.affiliation: VIB Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Martin
authors.initials: M
authors.lastname: Guilliams
authors.affiliation: Receptor Research Laboratories, Nuclear Receptor Lab, VIB Center for Medical Biotechnology, Ghent, Belgium; Department of Biochemistry, Ghent University, Ghent, Belgium.
authors.forename: Karolien
authors.initials: K
authors.lastname: De Bosscher
authors.affiliation: VIB Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine, Ghent University, Ghent, Belgium; Department of Pulmonary Medicine, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands.
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.affiliation: VIB Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine, Ghent University, Ghent, Belgium. Electronic address: hamida.hammad@ugent.be.
authors.forename: Hamida
authors.initials: H
authors.lastname: Hammad
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D039741:Antigens, Dermatophagoides / Q000276:immunology; D060829:Arthropod Proteins / Q000276:immunology; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology*; D050835:Interferon Regulatory Factors / Q000378:metabolism*; D007801:Langerhans Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D039981:Pyroglyphidae / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012867:Skin / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D000099218:Interferon Regulatory Factor-4
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D003546:Cysteine Endopeptidases; D050835:Interferon Regulatory Factors; D011948:Receptors, Antigen, T-Cell; D000099218:Interferon Regulatory Factor-4; C451162:Dermatophagoides pteronyssinus antigen p 1
keywords: Epicutaneous sensitization; airway inflammation; allergy; house dust mite; skin dendritic cells