Spi-B alleviates food allergy by securing mucosal barrier and immune tolerance in the intestine

Narumi Ishihara; Yutaka Nakamura; Kyosuke Yakabe; Seiga Komiyama; Yumiko Fujimura; Tsuneyasu Kaisho; Shunsuke Kimura; Koji Hase

doi:10.3389/falgy.2022.996657

Spi-B alleviates food allergy by securing mucosal barrier and immune tolerance in the intestine

Front Allergy. 2022 Oct 6:3:996657. doi: 10.3389/falgy.2022.996657. eCollection 2022.

Authors

Narumi Ishihara¹, Yutaka Nakamura^{1

2}, Kyosuke Yakabe¹, Seiga Komiyama¹, Yumiko Fujimura¹, Tsuneyasu Kaisho^{3

4}, Shunsuke Kimura^{1

5}, Koji Hase^{1

6

7}

Affiliations

¹ Division of Biochemistry, Faculty of Pharmacy, School of Pharmaceutical Sciences, Keio University, Tokyo, Japan.
² Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan.
³ Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan.
⁴ Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Japan.
⁵ Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Saitama, Japan.
⁶ Institute of Fermentation Sciences (IFeS), Faculty of Food and Agricultural Sciences, Fukushima University, Fukushima, Japan.
⁷ International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo (IMSUT), Tokyo, Japan.

Abstract

Food allergy is a type I allergic reaction induced by mast cells and is mainly activated by allergen-specific immunoglobulin (Ig)E. Spi-B is an E26-transformation-specific (Ets) family transcription factor essential for the differentiation and functional maturation of several immune cell subsets, including mast cells. However, the possible involvement of Spi-B in food allergy remains unclear. In this study, we found that Spi-B-deficient mice were highly susceptible to food allergy to ovalbumin (OVA), as indicated by the exacerbation of diarrhea and elevation of serum IgE levels. These pathological changes were associated with enhanced mast cell infiltration into the intestinal lamina propria. Activation of mast cells in the intestinal mucosa was observed in Spib ^-/- mice, even under physiological conditions. Accordingly, Spi-B deficiency increased the translocation of fluorescently labeled dextran from the lumen to the serum, suggesting increased intestinal permeability in Spib ^-/- mice. Moreover, Spib ^-/- mice showed defects in oral tolerance induction to OVA. These data illustrate that Spi-B suppresses the development of food allergies by controlling the activation of intestinal mast cells and by inducing immune tolerance to food allergens.

Keywords: IgE; Spi-B; epithelial barrier; food allergy; oral tolerance.