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J Allergy Clin Immunol. 2019 Oct;144(4):1058-1073.e3. doi: 10.1016/j.jaci.2019.04.030. Epub 2019 Jun 5.

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

Author information

1
Mary H. Weiser Food Allergy Center, Department of Pathology, University of Michigan, Ann Arbor, Mich; Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
2
Division of Gastroenterology, Washington University School of Medicine St Louis, St Louis, Mo.
3
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
4
Division of Clinical Engineering, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
5
Division of Pulmonary Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
6
Mary H. Weiser Food Allergy Center, Department of Pathology, University of Michigan, Ann Arbor, Mich.
7
Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
8
Division of Pediatric Surgery, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
9
Mary H. Weiser Food Allergy Center, Department of Pathology, University of Michigan, Ann Arbor, Mich; Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: sihogan@med.umich.edu.

Abstract

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.

KEYWORDS:

Food allergy; anaphylaxis; antigen passages; intestinal epithelium; mast cells; secretory cells

PMID:
31175877
PMCID:
PMC6779525
[Available on 2020-10-01]
DOI:
10.1016/j.jaci.2019.04.030

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