Inhibition of Pathologic Immunoglobulin E In Food Allergy by EBF2 and Active Compound Berberine Associated with Immunometabolism Regulation

Author Type(s)

Faculty

Document Type

Abstract

Publication Date

2-2023

DOI

10.1016/j.jaci.2022.12.708

Journal Title

Journal of Allergy and Clinical Immunology

Department

Pathology, Microbiology and Immunology

Abstract

Rationale

Food allergy is a significant public health problem with limited treatment options. As Food Allergy Herbal Formula 2 (FAHF-2) showed potential for a food allergy treatment, we further developed a purified version named EBF2 and identified active compounds. We investigated the mechanisms of EBF2 on IgE-mediated peanut (PN) allergy and its active compound, berberine, on IgE production.

Methods

IgE plasma cell line U266 cells were cultured with FAHF-2 and EBF2, and their effects on IgE production were compared. EBF2 was evaluated in a murine PN allergy model for its effect on PN-specific IgE production, number of IgE+ plasma cells, and PN anaphylaxis. Effects of berberine on IgE production, the expression of transcription factors, and mitochondrial glucose metabolism in U266 cells were evaluated.

Results

EBF2 dose-dependently suppressed IgE production and was over 16 times more potent than FAHF-2 in IgE suppression in U266 cells. EBF2 significantly suppressed PN-specific IgE production (70%, p<0.001) and the number of IgE-producing plasma cells in PN allergic mice, accompanied by 100% inhibition of PN-induced anaphylaxis and plasma histamine release (p<0.001) without affecting IgG1 or IgG2a production. Berberine markedly suppressed IgE production, which was associated with suppression of XBP1, BLIMP1, and STAT6 transcription factors and a reduced rate of mitochondrial oxidation in an IgE-producing plasma cell line.

Conclusions

EBF2 and its active compound berberine are potent IgE suppressors, associated with cellular regulation of immunometabolism on IgE plasma cells, and may be a potential therapy for IgE-mediated food allergy and other allergic disorders.

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