IKKβ in intestinal epithelial cells regulates allergen-specific IgA and allergic inflammation at distant mucosal sites
| Autor: | Ian C. Davis, Yan Sun, Famke Aeffner, Astrid Bonnegarde-Bernard, Mingqun Lin, Michael J. Fial, Junbae Jee, Prosper N. Boyaka, Daniel Tomé, Michael Karin, Estelle Cormet-Boyaka |
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| Přispěvatelé: | Department of Veterinary Biosciences [Colombus], College of Veterinary Medicine [Colombus], Ohio State University [Columbus] (OSU)-Ohio State University [Columbus] (OSU), Physiologie de la Nutrition et du Comportement Alimentaire (PNCA), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Department of Internal Medicine [Colombus], Ohio State University [Columbus] (OSU), Department of Pharmacology, University of California, Institut National de la Recherche Agronomique (INRA)-AgroParisTech |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
CD4-Positive T-Lymphocytes
Immunoglobulin A Cholera Toxin [SDV]Life Sciences [q-bio] Respiratory System Immunology Immunoglobulin E digestive system Article Allergic inflammation Allergic sensitization Mice 03 medical and health sciences 0302 clinical medicine Immune system Adjuvants Immunologic Intestinal mucosa Antigen Antibody Specificity Animals Immunology and Allergy Intestinal Mucosa ComputingMilieux_MISCELLANEOUS 030304 developmental biology Inflammation 0303 health sciences biology Interleukin-17 Allergens Immunity Innate I-kappa B Kinase 3. Good health biology.protein Dysbiosis Immunization Interleukin 17 Gene Deletion Signal Transduction 030215 immunology |
| Zdroj: | Mucosal Immunology Mucosal Immunology, Nature Pub. Group, 2014, 7 (2), pp.257-267. ⟨10.1038/mi.2013.43⟩ Mucosal immunology |
| ISSN: | 1933-0219 1935-3456 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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