title: Abnormal apical-to-basal transport of dietary ovalbumin by secretory IgA stimulates a mucosal Th1 response.
abstract: In celiac disease, enhanced permeability to gliadin peptides can result from their apico-basal transport by secretory immunoglobulin A1 (SIgA1) binding to the CD71 receptor ectopically expressed at the gut epithelial surface. Herein, we have established a mouse model in which there is apico-basal transport of the model antigen ovalbumin (OVA) by specific SIgA1 and have analyzed local T-cell activation. Transgenic DO11.10 mice were grafted with a hybridoma-secreting OVA-specific humanized IgA1, which could bind mouse CD71 and which were released in the intestinal lumen as SIgA. CD71 expression was induced at the gut apical surface by treating the mice with tyrphostin A8. Following gavage of the mice with OVA, OVA-specific CD4⁺ T cells isolated from the mesenteric lymph nodes displayed higher expression of the activation marker CD69 and produced more interferon gamma in mice bearing the hybridoma-secreting OVA-specific IgA1, than in ungrafted mice or in mice grafted with an irrelevant hybridoma. These results indicate that the protective role of SIgA1 might be jeopardized in human pathological conditions associated with ectopic expression of CD71 at the gut surface.
authors.affiliation: 1] Institut National de la Santé et de la Recherche Médicale (INSERM), UMR989, Paris, France [2] Université Paris Descartes-Sorbonne Paris Cité, Institut IMAGINE, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Abed
authors.affiliation: 1] Institut National de la Santé et de la Recherche Médicale (INSERM), UMR989, Paris, France [2] Université Paris Descartes-Sorbonne Paris Cité, Institut IMAGINE, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Lebreton
authors.affiliation: B Cell Design, rue C. Legendre, Limoges, France.
authors.forename: G
authors.initials: G
authors.lastname: Champier
authors.affiliation: B Cell Design, rue C. Legendre, Limoges, France.
authors.forename: A
authors.initials: A
authors.lastname: Cuvillier
authors.affiliation: CNRS, UMR6101 Université de Limoges, Limoges, France.
authors.forename: M
authors.initials: M
authors.lastname: Cogné
authors.affiliation: 1] Institut National de la Santé et de la Recherche Médicale (INSERM), UMR989, Paris, France [2] Université Paris Descartes-Sorbonne Paris Cité, Institut IMAGINE, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Meresse
authors.affiliation: Commissariat à l'Énergie Atomique, iBiTecS, Service d'Ingénierie Moléculaire des Protéines, Gif-sur-Yvette, France.
authors.forename: C
authors.initials: C
authors.lastname: Dugave
authors.affiliation: 1] Université Paris Descartes-Sorbonne Paris Cité, Institut IMAGINE, Paris, France [2] IFR 94, Imagery platform, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Garfa-Traoré
authors.affiliation: R&D Laboratory, Division of Immunology and Allergy, University State Hospital (CHUV), Lausanne, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Corthésy
authors.affiliation: 1] Institut National de la Santé et de la Recherche Médicale (INSERM), UMR989, Paris, France [2] Université Paris Descartes-Sorbonne Paris Cité, Institut IMAGINE, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Cerf-Bensussan
authors.affiliation: 1] Institut National de la Santé et de la Recherche Médicale (INSERM), UMR989, Paris, France [2] Université Paris Descartes-Sorbonne Paris Cité, Institut IMAGINE, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Heyman
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002446:Celiac Disease / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000276:immunology* / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology; D008643:Mesentery; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D011990:Receptors, Transferrin / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D020032:Tyrphostins / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015703:Antigens, CD; C068126:CD71 antigen; D007071:Immunoglobulin A, Secretory; D011990:Receptors, Transferrin; D020032:Tyrphostins; D010047:Ovalbumin