Histamine-releasing factor: a promising therapeutic target for food allergy
Marsha Wills-Karp
Marsha Wills-Karp
Published November 13, 2017
Citation Information: J Clin Invest. 2017;127(12):4238-4241. https://doi.org/10.1172/JCI98297.
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Commentary

Histamine-releasing factor: a promising therapeutic target for food allergy

Abstract

The prevalence of food allergies has been increasing at an alarming rate over the last few decades. Despite the dramatic increase in disease prevalence, the development of effective therapies has not kept pace. In this issue of the JCI, Ando et al. provide a causal link between histamine-releasing factor (HRF) interactions with IgE and food allergy in a murine model. Successful oral immunotherapy of both egg-allergic human patients and food-allergic mice was associated with sustained suppression of HRF-reactive IgE levels. These results support a role for HRF-IgE interactions in the amplification of intestinal inflammation and suggest HRF as a therapeutic target in food allergy.

Authors

Marsha Wills-Karp

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Figure 1

HRF amplifies the allergic response.

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HRF amplifies the allergic response. Exposure to food allergen results i...
Exposure to food allergen results in release of inflammatory cytokines, including IL-33 and TSLP, from the epithelium, which in turn promotes the development of a Th2 inflammatory response that results in release of IL-4 and IL-13 and the development of food allergen–specific IgE. IL-4, IL-13, and IL-33 induce secretion of HRF from the intestinal epithelium and underlying fibroblasts. HRF dimerization is thought to crosslink IgE and enhance binding and activation of mast cells and basophils via FcRI. Activation of these cells results in the release of histamine, IL-4, and IL-13, thereby resulting in allergic inflammation, such as is observed in food allergy, asthma, and allergic rhinitis. Additionally, release of IL-4 and IL-13 from mast cells and basophils further exacerbates the allergic response by maintaining HRF secretion.