Eosinophils Promote Generation and Maintenance of Immunoglobulin-A-Expressing Plasma Cells and Contribute to Gut Immune Homeostasis
Eosinophils Promote Generation and Maintenance of Immunoglobulin-A-Expressing Plasma Cells and Contribute to Gut Immune Homeostasis
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DOI：
10.1016/j.immuni.2014.02.014
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发表时间：
2014-04-17
期刊：
影响因子：
32.4
通讯作者：
Berek, Claudia
中科院分区：
文献类型：
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作者：
Chu, Van Trung;Beller, Alexander;Berek, Claudia
虽然在正常的固有层（LP）中存在大量嗜酸性粒细胞，但它们在稳态粘膜免疫中的作用尚不清楚。在这里，我们表明嗜酸性粒细胞是维持肠道相关组织免疫稳态所必需的。通过使用嗜酸性粒细胞缺失的Delta dblGATA-1和PHIL小鼠或嗜酸性粒细胞特异性耗损模型，我们发现免疫球蛋白a (+) （IgA(+)）浆细胞数量和分泌的IgA减少。嗜酸性粒细胞缺乏的小鼠也表现出肠粘膜屏障的缺陷和肠道内微生物群组成的改变。此外，tgf - β依赖性事件，包括Peyer's patches （PP）中的类转换到IgA， CD103(+) T细胞包括Foxp3（+）调节性（Treg）的形成，以及CD103（+）树突状细胞的形成受到干扰。体外培养表明，嗜酸性粒细胞产生促进t非依赖性IgA类转换的因子。我们的研究结果表明，嗜酸性粒细胞是肠道相关组织免疫稳态的重要参与者，并进一步表明嗜酸性粒细胞可以促进组织完整性。
Although in normal lamina propria (LP) large numbers of eosinophils are present, little is known about their role in mucosal immunity at steady state. Here we show that eosinophils are needed to maintain immune homeostasis in gut-associated tissues. By using eosinophil-deficient Delta dblGATA-1 and PHIL mice or an eosinophil-specific depletion model, we found a reduction in immunoglobulin A(+) (IgA(+)) plasma cell numbers and in secreted IgA. Eosinophil-deficient mice also showed defects in the intestinal mucous shield and alterations in microbiota composition in the gut lumen. In addition, TGF-beta-dependent events including class switching to IgA in Peyer's patches (PP), the formation of CD103(+) T cells including Foxp3(+) regulatory (Treg), and also CD103(+) dendritic cells were disturbed. In vitro cultures showed that eosinophils produce factors that promote T-independent IgA class switching. Our findings show that eosinophils are important players for immune homeostasis in gut-associated tissues and add to data suggesting that eosinophils can promote tissue integrity.