Deutsches Rheuma Forschungszentrum Berlin, a Leibniz Institute, 10117 Berlin, Germany.
Institut für Immunologie, Veterinärmedizin, Freie Universität Berlin, 14163 Berlin, Germany.
Immunity. 2014 Apr 17;40(4):582-93. doi: 10.1016/j.immuni.2014.02.014.
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 ΔdblGATA-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-β-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.
尽管在正常的固有层（LP）中有大量的嗜酸性粒细胞存在，但对于它们在稳态下黏膜免疫中的作用知之甚少。在这里，我们表明嗜酸性粒细胞对于维持肠道相关组织中的免疫稳态是必需的。通过使用嗜酸性粒细胞缺陷型ΔdblGATA-1 和 PHIL 小鼠或嗜酸性粒细胞特异性耗竭模型，我们发现 IgA(+)浆细胞数量和分泌型 IgA 减少。嗜酸性粒细胞缺陷型小鼠还表现出肠道黏膜屏蔽缺陷和肠道腔中微生物群落组成改变。此外，TGF-β 依赖性事件，包括在派尔集合淋巴结（PP）中向 IgA 的类别转换、形成包括 Foxp3+调节性（Treg）在内的 CD103+T 细胞以及 CD103+树突状细胞都受到干扰。体外培养表明，嗜酸性粒细胞产生促进 T 细胞非依赖性 IgA 类别转换的因子。我们的研究结果表明，嗜酸性粒细胞是肠道相关组织中免疫稳态的重要参与者，并补充了表明嗜酸性粒细胞可以促进组织完整性的数据。
