Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Amsterdam University Medical Center, University of Amsterdam, Department of Gastroenterology and Hepatology and Tygat Institute for Liver and Intestinal Research, Meibergdreef 9, Amsterdam, Netherlands.
Science. 2019 Mar 1;363(6430):993-998. doi: 10.1126/science.aat7186.
Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype found at mucosal surfaces, where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IECs). IgA is induced by both T cell-dependent and -independent (TI) pathways. However, little is known about TI regulation. We report that IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response, which is protective against enteric inflammation. IEC ER stress causes TI and microbiota-independent expansion and activation of peritoneal B1b cells, which culminates in increased lamina propria and luminal IgA. Increased numbers of IgA-producing plasma cells were observed in healthy humans with defective autophagy, who are known to exhibit IEC ER stress. Upon ER stress, IECs communicate signals to the peritoneum that induce a barrier-protective TI IgA response.
免疫球蛋白 A（IgA）是在黏膜表面发现的主要分泌型免疫球蛋白同种型，它调节微生物共生并防止腔内容物与肠上皮细胞（IEC）接触。IgA 由 T 细胞依赖性和非依赖性（TI）途径诱导。然而，关于 TI 的调节知之甚少。我们报告称，IEC 内质网（ER）应激会诱导多反应性 IgA 反应，这对肠道炎症具有保护作用。IEC ER 应激导致 TI 和微生物群非依赖性的腹膜 B1b 细胞的扩增和激活，最终导致固有层和腔道 IgA 增加。在已知存在 IEC ER 应激的具有缺陷自噬的健康人中，观察到产生 IgA 的浆细胞数量增加。在 ER 应激时，IEC 向腹膜传递信号，诱导屏障保护性 TI IgA 反应。
