title: Dysbiosis and Staphylococcus aureus Colonization Drives Inflammation in Atopic Dermatitis.
abstract: Staphylococcus aureus skin colonization is universal in atopic dermatitis and common in cancer patients treated with epidermal growth factor receptor inhibitors. However, the causal relationship of dysbiosis and eczema has yet to be clarified. Herein, we demonstrate that Adam17(fl/fl)Sox9-(Cre) mice, generated to model ADAM17-deficiency in human, developed eczematous dermatitis with naturally occurring dysbiosis, similar to that observed in atopic dermatitis. Corynebacterium mastitidis, S. aureus, and Corynebacterium bovis sequentially emerged during the onset of eczematous dermatitis, and antibiotics specific for these bacterial species almost completely reversed dysbiosis and eliminated skin inflammation. Whereas S. aureus prominently drove eczema formation, C. bovis induced robust T helper 2 cell responses. Langerhans cells were required for eliciting immune responses against S. aureus inoculation. These results characterize differential contributions of dysbiotic flora during eczema formation, and highlight the microbiota-host immunity axis as a possible target for future therapeutics in eczematous dermatitis.
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan, PC160-8582; Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Glatz
authors.affiliation: Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan, PC160-8582.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Horiuchi
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan, PC160-8582.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawasaki
authors.affiliation: Department of Orthopedics, Gifu University, Gifu, Japan, PC 501-1194.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
authors.affiliation: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, MN 55414, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Kaplan
authors.affiliation: Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Heidi H
authors.initials: HH
authors.lastname: Kong
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan, PC160-8582.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Amagai
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan, PC160-8582; Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: keisuke.nagao@nih.gov.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nagao
mesh_terms: D051722:ADAM Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D000072198:ADAM17 Protein; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003352:Corynebacterium / Q000276:immunology; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D064806:Dysbiosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D004485:Eczema / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D066246:ErbB Receptors / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D019426:Integrases / Q000235:genetics / Q000276:immunology; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D012867:Skin / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; C541485:EGFR protein, mouse; D066246:ErbB Receptors; C045073:Cre recombinase; D019426:Integrases; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse