title: IKKβ in intestinal epithelial cells regulates allergen-specific IgA and allergic inflammation at distant mucosal sites.
abstract: Regulation of allergic responses by intestinal epithelial cells (IECs) remains poorly understood. Using a model of oral allergen sensitization in the presence of cholera toxin as adjuvant and mice with cell-specific deletion of inhibitor-κB kinase (IKKβ) in IECs (IKKβ(ΔIEC)), we addressed the contribution of IECs to allergic sensitization to ingested antigens and allergic manifestations at distant mucosal site of the airways. Cholera toxin induced higher pro-inflammatory responses and altered the profile of the gut microbiota in IKKβ(ΔIEC) mice. Antigen-specific immunoglobulin E (IgE) responses were unaltered in IKKβ(ΔIEC) mice, but their IgA antibodies (Abs), T helper type 1 (Th1) and Th17 responses were enhanced. Upon nasal antigen challenge, these mice developed lower levels of allergic lung inflammation, which correlated with higher levels of IgA Abs in the airways. The IKKβ(ΔIEC) mice also recruited a higher number of gut-sensitized T cells in the airways after nasal antigen challenge and developed airway hyper-responsiveness, which were suppressed by treatment with anti-interleukin-17A. Fecal microbiota transplant during allergic sensitization reduced Th17 responses in IKKβ(ΔIEC) mice, but did not affect IgA Ab responses. In summary, we show that IKKβ in IECs shapes the gut microbiota and immune responses to ingested antigens and influences allergic responses in the airways via regulation of IgA Ab responses.
authors.affiliation: 1] Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA [2] Laboratory of Human Nutrition, Agro Paris Tech, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Bonnegarde-Bernard
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA.
authors.forename: J
authors.initials: J
authors.lastname: Jee
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Fial
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA.
authors.forename: F
authors.initials: F
authors.lastname: Aeffner
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA.
authors.forename: E
authors.initials: E
authors.lastname: Cormet-Boyaka
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA.
authors.forename: I C
authors.initials: IC
authors.lastname: Davis
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA.
authors.forename: M
authors.initials: M
authors.lastname: Lin
authors.affiliation: Laboratory of Human Nutrition, Agro Paris Tech, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Tomé
authors.affiliation: Department of Pharmacology, University of California, La Jolla, California, USA.
authors.forename: M
authors.initials: M
authors.lastname: Karin
authors.affiliation: Research and Testing Laboratory, Lubbock, Texas, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.affiliation: 1] Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA [2] Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA.
authors.forename: P N
authors.initials: PN
authors.lastname: Boyaka
mesh_terms: D000276:Adjuvants, Immunologic; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002772:Cholera Toxin / Q000276:immunology; D064806:Dysbiosis / Q000276:immunology; D017353:Gene Deletion; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007114:Immunization; D007070:Immunoglobulin A / Q000276:immunology*; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism*; D020381:Interleukin-17 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D012137:Respiratory System / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; D007070:Immunoglobulin A; D020381:Interleukin-17; D002772:Cholera Toxin; D051550:I-kappa B Kinase