Histamine-releasing factor enhances food allergy

Histamine-Releasing Factor, a New Therapeutic Target in Allergic Diseases

“…Consistent with the efficacy of HRF inhibitors in allergic disease models (see below), IgE-binding sequences (i.e., N19 and H3) are exposed on the molecular surface of HRF dimer (Figure 1a,b) [28]. Recombinant HRF homodimers, but not monomers, synthesized in E. coli can activate murine mast cells [30]. GST-HRF fusion proteins induce not only histamine release [8] but also secretion of IL-4 and IL-13 from human basophils [15,16].…”

“…Thus, this study in 2012 solved several major questions about HRF, including the aforementioned issues (i) and (ii). More recently, Ando et al showed that HRF dimers, but not monomers, are able to activate HRF-reactive IgE-bound mast cells and basophils [30]. Intragastric administration of HRF inhibitors, which preferentially targeted mast cells in the small intestine, strongly reduced diarrhea occurrence, intestinal inflammation, and systemic anaphylaxis in a murine model of food allergy [30,43].…”

“…More recently, Ando et al showed that HRF dimers, but not monomers, are able to activate HRF-reactive IgE-bound mast cells and basophils [30]. Intragastric administration of HRF inhibitors, which preferentially targeted mast cells in the small intestine, strongly reduced diarrhea occurrence, intestinal inflammation, and systemic anaphylaxis in a murine model of food allergy [30,43]. Levels of HRF oligomers (including dimers) in the small intestine and HRF-reactive IgE in serum were increased in food allergic mice, but HRF oligomers were decreased by HRF inhibitors.…”

“…IL-4 derived from basophils stimulated by cytokines such as IL-33 seems to be required for Th2 cell differentiation [51], and IL-4 promotes intestinal mast cell accumulation and activation [52]. HRF dimer/oligomers secreted from several types of cells amplify intestinal inflammation by enhancing antigen/IgE-mediated activation of mast cells and basophils [30]. This is likely due to increased HRF secretion by several types of cells in response to Th2, proinflammatory and epithelial cytokines.…”

“…Interestingly, essentially all exosome-associated (and microparticle-associated) HRF in endothelial cells was dimeric [63]. However, there is no evidence that the function of intracellular TCTP molecules is operated by the dimeric form, as the vast majority of intracellular TCTP molecules is monomeric [30]. No definitive studies have been conducted to assign the functions of HRF/TCTP to either its monomeric or dimeric forms (or other forms) in PAH and other diseases.…”