title: Neutrophils are required for both the sensitization and elicitation phase of contact hypersensitivity.
abstract: Allergic contact dermatitis and its animal model, contact hypersensitivity (CHS), are T cell-mediated inflammatory skin diseases induced by contact allergens. Though numerous cellular and molecular players are known, the mechanism of chemical-induced sensitization remains poorly understood. Here, we identify neutrophils as crucial players in the sensitization phase of CHS. Genetic deficiency of neutrophils caused by myeloid-specific deletion of Mcl-1 or antibody-mediated depletion of neutrophils before sensitization abrogated the CHS response. Neutrophil deficiency reduced contact allergen-induced cytokine production, gelatinase release, and reactive oxygen species production in naive mice. Mast cell deficiency inhibited neutrophil accumulation at the site of sensitization. In turn, neutrophils were required for contact allergen-induced release of further neutrophil-attracting chemokines, migration of DCs to the draining lymph nodes, and priming of allergen-specific T cells. Lymph node cells from mice sensitized in the absence of neutrophils failed to transfer sensitization to naive recipients. Furthermore, no CHS response could be induced when neutrophils were depleted before elicitation or when normally sensitized lymph node cells were transferred to neutrophil-deficient recipients, indicating an additional role for neutrophils in the elicitation phase. Collectively, our data identify neutrophils to be critically involved in both the sensitization and elicitation phase of CHS.
authors.affiliation: Allergy Research Group, Department of Dermatology, Medical Center, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany Allergy Research Group, Department of Dermatology, Medical Center, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany Department of Physiology, Semmelweis University School of Medicine; MTA-SE "Lendület" Inflammation Physiology Research Group of the Hungarian Academy of Sciences and the Semmelweis University, 1094 Budapest, Hungary.
authors.forename: Felix C
authors.initials: FC
authors.lastname: Weber
authors.affiliation: Department of Physiology, Semmelweis University School of Medicine; MTA-SE "Lendület" Inflammation Physiology Research Group of the Hungarian Academy of Sciences and the Semmelweis University, 1094 Budapest, Hungary Department of Physiology, Semmelweis University School of Medicine; MTA-SE "Lendület" Inflammation Physiology Research Group of the Hungarian Academy of Sciences and the Semmelweis University, 1094 Budapest, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Németh
authors.affiliation: Department of Physiology, Semmelweis University School of Medicine; MTA-SE "Lendület" Inflammation Physiology Research Group of the Hungarian Academy of Sciences and the Semmelweis University, 1094 Budapest, Hungary Department of Physiology, Semmelweis University School of Medicine; MTA-SE "Lendület" Inflammation Physiology Research Group of the Hungarian Academy of Sciences and the Semmelweis University, 1094 Budapest, Hungary.
authors.forename: Janka Z
authors.initials: JZ
authors.lastname: Csepregi
authors.affiliation: Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Dudeck
authors.affiliation: Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, 01307 Dresden, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Roers
authors.affiliation: Avidin Ltd., 6726 Szeged, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Ozsvári
authors.affiliation: Allergy Research Group, Department of Dermatology, Medical Center, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Oswald
authors.affiliation: Avidin Ltd., 6726 Szeged, Hungary.
authors.forename: László G
authors.initials: LG
authors.lastname: Puskás
authors.affiliation: Allergy Research Group, Department of Dermatology, Medical Center, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Jakob
authors.affiliation: Department of Physiology, Semmelweis University School of Medicine; MTA-SE "Lendület" Inflammation Physiology Research Group of the Hungarian Academy of Sciences and the Semmelweis University, 1094 Budapest, Hungary Department of Physiology, Semmelweis University School of Medicine; MTA-SE "Lendület" Inflammation Physiology Research Group of the Hungarian Academy of Sciences and the Semmelweis University, 1094 Budapest, Hungary stefan.martin@uniklinik-freiburg.de mocsai.attila@med.semmelweis-univ.hu.
authors.forename: Attila
authors.initials: A
authors.lastname: Mócsai
authors.affiliation: Allergy Research Group, Department of Dermatology, Medical Center, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany stefan.martin@uniklinik-freiburg.de mocsai.attila@med.semmelweis-univ.hu.
authors.forename: Stefan F
authors.initials: SF
authors.lastname: Martin
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology; D053818:Chymases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D017382:Reactive Oxygen Species; C509227:Cma1 protein, mouse; D053818:Chymases