title: Critical role for syndecan-4 in dendritic cell migration during development of allergic airway inflammation.
abstract: Syndecan-4 (SDC4), expressed on dendritic cells (DCs) and activated T cells, plays a crucial role in DC motility and has been shown as a potential target for activated T-cell-driven diseases. In the present study, we investigate the role of SDC4 in the development of T-helper 2 cell-mediated allergic asthma. Using SDC4-deficient mice or an anti-SDC4 antibody we show that the absence or blocking of SDC4 signalling in ovalbumin-sensitized mice results in a reduced asthma phenotype compared with control animals. Most importantly, even established asthma is significantly decreased using the anti-SDC4 antibody. The disturbed SDC4 signalling leads to an impaired motility and directional migration of antigen-presenting DCs and therefore, to a modified sensitization leading to diminished airway inflammation. Our results demonstrate that SDC4 plays an important role in asthma induction and indicate SDC4 as possible target for therapeutic intervention in this disease.
authors.affiliation: Department of Environmental Immunology, UFZ-Helmholtz Centre for Environmental Research Leipzig-Halle, Permoserstrasse 15, Leipzig 04318, Germany.|Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, Leipzig 04103, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Polte
authors.affiliation: Department of Environmental Immunology, UFZ-Helmholtz Centre for Environmental Research Leipzig-Halle, Permoserstrasse 15, Leipzig 04318, Germany.|Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, Leipzig 04103, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Petzold
authors.affiliation: Institute for Experimental Musculoskeletal Medicine, University Hospital Münster, Münster 48149, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Bertrand
authors.affiliation: Department of Environmental Immunology, UFZ-Helmholtz Centre for Environmental Research Leipzig-Halle, Permoserstrasse 15, Leipzig 04318, Germany.|Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, Leipzig 04103, Germany.|LIFE-Leipzig Research Center for Civilization Diseases, Leipzig University, Leipzig 04103, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schütze
authors.affiliation: Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, Leipzig 04103, Germany.|LIFE-Leipzig Research Center for Civilization Diseases, Leipzig University, Leipzig 04103, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Hinz
authors.affiliation: Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, Leipzig 04103, Germany.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Simon
authors.affiliation: Department of Environmental Immunology, UFZ-Helmholtz Centre for Environmental Research Leipzig-Halle, Permoserstrasse 15, Leipzig 04318, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Lehmann
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover 30625, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Echtermeyer
authors.affiliation: Institute for Experimental Musculoskeletal Medicine, University Hospital Münster, Münster 48149, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pap
authors.affiliation: Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, Leipzig 04103, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Averbeck
mesh_terms: D000276:Adjuvants, Immunologic; D000536:Aluminum Hydroxide; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D008276:Magnesium Hydroxide; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin; D010991:Plethysmography; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D053671:Syndecan-4 / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D007074:Immunoglobulin G; C508306:Sdc4 protein, mouse; D053671:Syndecan-4; D007073:Immunoglobulin E; D000536:Aluminum Hydroxide; D010047:Ovalbumin; D008276:Magnesium Hydroxide