title: Self-Antigen Presentation by Keratinocytes in the Inflamed Adult Skin Modulates T-Cell Auto-Reactivity.
abstract: Keratinocytes have a pivotal role in the regulation of immune responses, but the impact of antigen presentation by these cells is still poorly understood, particularly in a situation where the antigen will be presented only in adult life. Here, we generated a transgenic mouse model in which keratinocytes exclusively present a myelin basic protein (MBP) peptide covalently linked to the major histocompatibility complex class II β-chain, solely under inflammatory conditions. In these mice, inflammation caused by epicutaneous contact sensitizer treatment resulted in keratinocyte-mediated expansion of MBP-specific CD4(+) T cells in the skin. Moreover, repeated contact sensitizer application preceding a systemic MBP immunization reduced the reactivity of the respective CD4(+) T cells and lowered the symptoms of the resulting experimental autoimmune encephalomyelitis. This downregulation was CD4(+) T-cell-mediated and dependent on the presence of the immune modulator Dickkopf-3. Thus, presentation of a neo self-antigen by keratinocytes in the inflamed, adult skin can modulate CD4(+) T-cell auto-aggression at a distal organ.
authors.affiliation: Department of Molecular Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Meister
authors.affiliation: Department of Molecular Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Amel
authors.initials: A
authors.lastname: Tounsi
authors.affiliation: Department of Dermatology and Allergy, Laboratory of Experimental Dermatology, University of Bonn, Bonn, Germany.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Gaffal
authors.affiliation: Department of Dermatology and Allergy, Laboratory of Experimental Dermatology, University of Bonn, Bonn, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Bald
authors.affiliation: Department of Molecular Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Papatriantafyllou
authors.affiliation: Department of Molecular Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Ludwig
authors.affiliation: Department of Molecular Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Pougialis
authors.affiliation: Core Facility Light Microscopy, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Bestvater
authors.affiliation: Department of Neurology, Clinic for Neurology, University Hospital Münster, Münster, Germany.
authors.forename: Luisa
authors.initials: L
authors.lastname: Klotz
authors.affiliation: Department of Molecular Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Moldenhauer
authors.affiliation: Department of Dermatology and Allergy, Laboratory of Experimental Dermatology, University of Bonn, Bonn, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tüting
authors.affiliation: Department of Molecular Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Günter J
authors.initials: GJ
authors.lastname: Hämmerling
authors.affiliation: Department of Molecular Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: b.arnold@dkfz.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Arnold
authors.affiliation: Department of Molecular Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Oelert
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001324:Autoantigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D003521:Cyclopropanes / Q000494:pharmacology; D003872:Dermatitis / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control; D005802:Genes, MHC Class II / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000235:genetics; D010080:Oxazoles / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: C119678:4-ethoxymethylene-2-phenyl-2-oxazoline-5-one; D048868:Adaptor Proteins, Signal Transducing; D001324:Autoantigens; D003521:Cyclopropanes; C405061:Dkk3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D004676:Myelin Basic Protein; D010080:Oxazoles; C029402:diphenylcyclopropenone
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