Abnormal apical-to-basal transport of dietary ovalbumin by secretory IgA stimulates a mucosal Th1 response

Mucosal Immunol. 2014 Mar;7(2):315-24. doi: 10.1038/mi.2013.49. Epub 2013 Jul 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • Celiac Disease / immunology
  • Celiac Disease / metabolism
  • Disease Models, Animal
  • Enterocytes / drug effects
  • Enterocytes / metabolism
  • Female
  • Humans
  • Immunoglobulin A, Secretory / immunology*
  • Immunoglobulin A, Secretory / metabolism*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism*
  • Lymph Nodes / immunology
  • Mesentery
  • Mice
  • Mice, Transgenic
  • Ovalbumin / metabolism*
  • Protein Binding
  • Protein Transport
  • Receptors, Transferrin / metabolism
  • Th1 Cells / immunology*
  • Tyrphostins / pharmacology
  • Up-Regulation / drug effects

Substances

  • Antigens, CD
  • CD71 antigen
  • Immunoglobulin A, Secretory
  • Receptors, Transferrin
  • Tyrphostins
  • Ovalbumin