title: The absence of a microbiota enhances TSLP expression in mice with defective skin barrier but does not affect the severity of their allergic inflammation.
abstract: Evidence is accumulating to suggest that our indigenous microbial communities (microbiota) may have a role in modulating allergic and immune disorders of the skin. To examine the link between the microbiota and atopic dermatitis (AD), we examined a mouse model of defective cutaneous barrier function with an AD-like disease due to loss of Notch signaling. Comparisons of conventionally raised and germ-free (GF) mice revealed a similar degree of allergic skin inflammation, systemic atopy, and airway hypersensitivity. GF mutant animals expressed significantly higher levels of thymic stromal lymphopoietin, a major proinflammatory cytokine released by skin with defective barrier function, resulting in a more severe B-lymphoproliferative disorder that persisted into adulthood. These findings suggest a role for the microbiota in ameliorating stress signals released by keratinocytes in response to perturbation in cutaneous barrier function.
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Yockey
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Shadmehr
authors.initials: S
authors.lastname: Demehri
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Turkoz
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Ahu
authors.initials: A
authors.lastname: Turkoz
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Philip P
authors.initials: PP
authors.lastname: Ahern
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Omar
authors.initials: O
authors.lastname: Jassim
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Sindhu
authors.initials: S
authors.lastname: Manivasagam
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Kearney
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Gordon
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri, USA. Electronic address: Kopan@wustl.edu.
authors.forename: Raphael
authors.initials: R
authors.lastname: Kopan
mesh_terms: D000483:Alleles; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006967:Hypersensitivity / Q000378:metabolism*; D007073:Immunoglobulin E / Q000097:blood; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics; D007249:Inflammation / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota; D012867:Skin / Q000276:immunology* / Q000382:microbiology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497571:Rbpj protein, mouse; D007073:Immunoglobulin E; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse