title: A Wave of Regulatory T Cells into Neonatal Skin Mediates Tolerance to Commensal Microbes.
abstract: The skin is a site of constant dialog between the immune system and commensal bacteria. However, the molecular mechanisms that allow us to tolerate the presence of skin commensals without eliciting destructive inflammation are unknown. Using a model system to study the antigen-specific response to S. epidermidis, we demonstrated that skin colonization during a defined period of neonatal life was required for establishing immune tolerance to commensal microbes. This crucial window was characterized by an abrupt influx of highly activated regulatory T (Treg) cells into neonatal skin. Selective inhibition of this Treg cell wave completely abrogated tolerance. Thus, the host-commensal relationship in the skin relied on a unique Treg cell population that mediated tolerance to bacterial antigens during a defined developmental window. This suggests that the cutaneous microbiome composition in neonatal life is crucial in shaping adaptive immune responses to commensals, and disrupting these interactions might have enduring health implications.
authors.affiliation: Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Tiffany C
authors.initials: TC
authors.lastname: Scharschmidt
authors.affiliation: Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Kimberly S
authors.initials: KS
authors.lastname: Vasquez
authors.affiliation: Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Hong-An
authors.initials: HA
authors.lastname: Truong
authors.affiliation: Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Sofia V
authors.initials: SV
authors.lastname: Gearty
authors.affiliation: Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Mariela L
authors.initials: ML
authors.lastname: Pauli
authors.affiliation: Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Audrey
authors.initials: A
authors.lastname: Nosbaum
authors.affiliation: Department of Molecular Biology, University of Salzburg, 5020 Salzburg, Austria.
authors.forename: Iris K
authors.initials: IK
authors.lastname: Gratz
authors.affiliation: National Institute of Allergy and Infectious Disease, NIH, Bethesda, MD 20892, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Otto
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Moon
authors.affiliation: Institute for Medical Microbiology and Hygiene, University Hospital Tübingen, 72076 Tübingen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Liese
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Abul K
authors.initials: AK
authors.lastname: Abbas
authors.affiliation: Department of Bioengineering and Therapeutic Sciences and California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Fischbach
authors.affiliation: Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: michael.rosenblum@ucsf.edu.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Rosenblum
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology* / Q000382:microbiology; D000942:Antigens, Bacterial / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000276:immunology; D008969:Molecular Sequence Data; D012867:Skin / Q000276:immunology* / Q000382:microbiology*; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology; D013212:Staphylococcus epidermidis / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial