Spi-B alleviates food allergy by securing mucosal barrier and immune tolerance in the intestine.
Spi-B alleviates food allergy by securing mucosal barrier and immune tolerance in the intestine.
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DOI：
10.3389/falgy.2022.996657
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发表时间：
2022
影响因子：
--
通讯作者：
Hase, Koji
中科院分区：
文献类型：
--
作者：
Ishihara, Narumi;Nakamura, Yutaka;Yakabe, Kyosuke;Komiyama, Seiga;Fujimura, Yumiko;Kaisho, Tsuneyasu;Kimura, Shunsuke;Hase, Koji
食物过敏是由肥大细胞引起的I型变态反应，主要由过敏原特异性免疫球蛋白（IG）E激活。Spi-B是一种E26转化特异性（Ets）家族转录因子，对包括肥大细胞在内的几种免疫细胞亚群的分化和功能成熟至关重要。然而，Spi-B可能参与食物过敏仍不清楚。在这项研究中，我们发现，Spi-B-缺陷小鼠是高度敏感的食物过敏卵清蛋白（OVA），腹泻和血清IgE水平升高的加剧所示。这些病理变化与肠固有层肥大细胞浸润增强有关。在Spib −/−小鼠中观察到肠粘膜中肥大细胞的活化，即使在生理条件下也是如此。因此，Spi-B缺乏增加了荧光标记的葡聚糖从管腔到血清的移位，表明Spib −/−小鼠的肠道通透性增加。此外，Spib −/−小鼠在对OVA的口服耐受诱导中表现出缺陷。这些数据表明，Spi-B通过控制肠道肥大细胞的活化和诱导对食物过敏原的免疫耐受来抑制食物过敏的发展。
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.
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