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Article Dans Une Revue Journal of Allergy and Clinical Immunology Année : 2019

IL-13–induced intestinal secretory epithelial cell antigen passages are required for IgE-mediated food-induced anaphylaxis

Taeko K. Noah
  • Fonction : Auteur
Kathryn A. Knoop
  • Fonction : Auteur
Keely G. Mcdonald
  • Fonction : Auteur
Jenny K. Gustafsson
  • Fonction : Auteur
Lisa Waggoner
  • Fonction : Auteur
Simone Vanoni
  • Fonction : Auteur
Matthew Batie
  • Fonction : Auteur
Kavisha Arora
  • Fonction : Auteur
Anjaparavanda P. Naren
  • Fonction : Auteur
Yui-Hsi Wang
  • Fonction : Auteur
Nicholas W Lukacs
  • Fonction : Auteur
Ariel Munitz
Michael A. Helmrath
  • Fonction : Auteur
Rodney D. Newberry
  • Fonction : Auteur
Simon P. Hogan
  • Fonction : Auteur

Résumé

Background: Food-induced anaphylaxis (FIA) is an IgE-dependent immune response that can affect multiple organs and lead to life-threatening complications. The processes by which food allergens cross the mucosal surface and are delivered to the subepithelial immune compartment to promote the clinical manifestations associated with food-triggered anaphylaxis are largely unexplored. Objective: We sought to define the processes involved in the translocation of food allergens across the mucosal epithelial surface to the subepithelial immune compartment in FIA. Methods: Two-photon confocal and immunofluorescence microscopy was used to visualize and trace food allergen passage in a murine model of FIA. A human colon cancer cell line, RNA silencing, and pharmacologic approaches were used to identify the molecular regulation of intestinal epithelial allergen uptake and translocation. Human intestinal organoid transplants were used to demonstrate the conservation of these molecular processes in human tissues. Results: Food allergens are sampled by using small intestine (SI) epithelial secretory cells (termed secretory antigen passages [SAPs]) that are localized to the SI villous and crypt region. SAPs channel food allergens to lamina propria mucosal mast cells through an IL-13–CD38–cyclic adenosine diphosphate ribose (cADPR)–dependent process. Blockade of IL-13-induced CD38/cADPR-dependent SAP antigen passaging in mice inhibited induction of clinical manifestations of FIA. IL-13–CD38–cADPR–dependent SAP sampling of food allergens was conserved in human intestinal organoids. Conclusion: We identify that SAPs are a mechanism by which food allergens are channeled across the SI epithelium mediated by the IL-13/CD38/cADPR pathway, regulate the onset of FIA reactions, and are conserved in human intestine.

Dates et versions

hal-02533221 , version 1 (07-04-2020)

Identifiants

Citer

Taeko K. Noah, Kathryn A. Knoop, Keely G. Mcdonald, Jenny K. Gustafsson, Lisa Waggoner, et al.. IL-13–induced intestinal secretory epithelial cell antigen passages are required for IgE-mediated food-induced anaphylaxis. Journal of Allergy and Clinical Immunology, 2019, 144 (4), pp.1058-1073.e3. ⟨10.1016/j.jaci.2019.04.030⟩. ⟨hal-02533221⟩
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