title: Commensal-dendritic-cell interaction specifies a unique protective skin immune signature.
abstract: The skin represents the primary interface between the host and the environment. This organ is also home to trillions of microorganisms that play an important role in tissue homeostasis and local immunity. Skin microbial communities are highly diverse and can be remodelled over time or in response to environmental challenges. How, in the context of this complexity, individual commensal microorganisms may differentially modulate skin immunity and the consequences of these responses for tissue physiology remains unclear. Here we show that defined commensals dominantly affect skin immunity and identify the cellular mediators involved in this specification. In particular, colonization with Staphylococcus epidermidis induces IL-17A(+) CD8(+) T cells that home to the epidermis, enhance innate barrier immunity and limit pathogen invasion. Commensal-specific T-cell responses result from the coordinated action of skin-resident dendritic cell subsets and are not associated with inflammation, revealing that tissue-resident cells are poised to sense and respond to alterations in microbial communities. This interaction may represent an evolutionary means by which the skin immune system uses fluctuating commensal signals to calibrate barrier immunity and provide heterologous protection against invasive pathogens. These findings reveal that the skin immune landscape is a highly dynamic environment that can be rapidly and specifically remodelled by encounters with defined commensals, findings that have profound implications for our understanding of tissue-specific immunity and pathologies.
authors.affiliation: 1] Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, Bethesda 20892, USA [2] Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Shruti
authors.initials: S
authors.lastname: Naik
authors.affiliation: 1] Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, Bethesda 20892, USA [2] Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bouladoux
authors.affiliation: 1] Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, Bethesda 20892, USA [2] Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Linehan
authors.affiliation: 1] Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, Bethesda 20892, USA [2] Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Seong-Ji
authors.initials: SJ
authors.lastname: Han
authors.affiliation: 1] Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, Bethesda 20892, USA [2] Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Harrison
authors.affiliation: 1] Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, Bethesda 20892, USA [2] Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wilhelm
authors.affiliation: Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Conlan
authors.affiliation: 1] Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, Bethesda 20892, USA [2] Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Himmelfarb
authors.affiliation: 1] Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, Bethesda 20892, USA [2] Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA [3] Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA.
authors.forename: Allyson L
authors.initials: AL
authors.lastname: Byrd
authors.affiliation: Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA.
authors.forename: Clayton
authors.initials: C
authors.lastname: Deming
authors.affiliation: Bioinformatics and Computational Bioscience Branch, National Institute of Allergy and Infectious Diseases, NIH Bethesda, Maryland 20892, USA.
authors.forename: Mariam
authors.initials: M
authors.lastname: Quinones
authors.affiliation: 1] Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, Bethesda 20892, USA [2] Immunopathogenesis Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH Bethesda, Maryland 20892, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.affiliation: Dermatology Branch, National Cancer Institute, NIH Bethesda, Maryland 20892, USA.
authors.forename: Heidi H
authors.initials: HH
authors.lastname: Kong
authors.affiliation: Howard Hughes Medical Institute, Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
authors.forename: Roxanne
authors.initials: R
authors.lastname: Tussiwand
authors.affiliation: Howard Hughes Medical Institute, Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
authors.affiliation: Department of Oncological Sciences, Tisch Cancer Institute and Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
authors.affiliation: Translational and Functional Genomics Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Segre
authors.affiliation: 1] Immunity at Barrier Sites Initiative, National Institute of Allergy and Infectious Diseases, NIH, Bethesda 20892, USA [2] Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011323:Primates; D012867:Skin / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D013212:Staphylococcus epidermidis / Q000276:immunology; D013559:Symbiosis / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D020381:Interleukin-17