Epithelial endoplasmic reticulum stress orchestrates a protective IgA response II

Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype at mucosal surfaces where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IEC). IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response which protects from small intestinal inflammation. IEC ER stress causes expansion and activation of peritoneal B1b cells independent of microbiota and T cells that culminates in increased lamina propria and luminal IgA. Xbp1dIEC mice exhibit IEC ER stress by conditional deletion of X-box-binding protein 1 (XBP1). Here we examine single-cell transcriptomes of peritoneal cavity cells of germ-free Xbp1dIEC mice (KO) compared to littermate controls (WT). Overall design: Single-cell gene expression profiles of peritoneal cavity cells of 10-week-old germ-free Xbp1dIEC and WT mice were generated using a droplet-based system (10X Genomics Chromium).免疫球蛋白A（Immunoglobulin A, IgA）是黏膜表面的主要分泌型免疫球蛋白亚型，可调控微生物群共生，并阻挡肠腔因子与肠上皮细胞（intestinal epithelial cells, IEC）接触。肠上皮细胞内质网（endoplasmic reticulum, ER）应激可诱导多反应性IgA应答，从而发挥抵御小肠炎症的保护作用。肠上皮细胞内质网应激可独立于微生物群与T细胞，促进腹膜B1b细胞的扩增与活化，最终使固有层与肠腔中的IgA水平升高。Xbp1dIEC小鼠通过条件性敲除X盒结合蛋白1（X-box-binding protein 1, XBP1）构建，该小鼠可出现肠上皮细胞内质网应激。本研究对无菌Xbp1dIEC小鼠（KO组）与同窝野生型对照小鼠（WT组）的腹膜腔细胞开展了单细胞转录组分析。实验整体设计：采用微滴捕获系统（10× Genomics Chromium），制备10周龄无菌Xbp1dIEC与WT小鼠的腹膜腔细胞单细胞基因表达谱。