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J Clin Invest. 2017 Dec 1;127(12):4541-4553. doi: 10.1172/JCI96525. Epub 2017 Nov 13.

Histamine-releasing factor enhances food allergy.

Author information

1
Laboratory for Cytokine Regulation, RIKEN Center for Integrative Medical Sciences (RIKEN IMS), Yokohama, Japan.
2
Atopy Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
3
Laboratory for Intestinal Ecosystem, RIKEN IMS, Yokohama, Japan.
4
Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu, Japan.
5
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
6
Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
7
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama, Japan.
8
Department of Education for Childcare, Faculty of Child Studies, Tokyo Kasei University, Tokyo, Japan.
9
Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, Japan.
10
Department of Pediatrics and Allergy and.
11
Institute for Clinical Research, Mie National Hospital, Tsu, Mie, Japan.
12
Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
13
Department of Dermatology, UCSD, School of Medicine, La Jolla, California, USA.

Abstract

Food allergy occurs due to IgE- and mast cell-dependent intestinal inflammation. Previously, we showed that histamine-releasing factor (HRF), a multifunctional protein secreted during allergy, interacts with a subset of IgE molecules and that the HRF dimer activates mast cells in an HRF-reactive IgE-dependent manner. In this study, we investigated whether HRF plays any role in food allergy. Specifically, we determined that prophylactic and therapeutic administration of HRF inhibitors that block HRF-IgE interactions reduces the incidence of diarrhea and mastocytosis in a murine model of food allergy. Food allergy-associated intestinal inflammation was accompanied by increased secretion of the HRF dimer into the intestine in response to proinflammatory, Th2, and epithelial-derived cytokines and HRF-reactive IgE levels at the elicitation phase. Consistent with these data, patients with egg allergy had higher blood levels of HRF-reactive IgE compared with individuals that were not hypersensitive. Successful oral immunotherapy in egg-allergy patients and food-allergic mice reduced HRF-reactive IgE levels, thereby suggesting a pathological role for HRF in food allergy. Together, these results suggest that antigen and HRF dimer amplify intestinal inflammation by synergistically activating mast cells and indicate that HRF has potential as a therapeutic target in food allergy.

KEYWORDS:

Allergy; Inflammation

PMID:
29130935
PMCID:
PMC5707161
DOI:
10.1172/JCI96525
[Indexed for MEDLINE]
Free PMC Article

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