Epithelial endoplasmic reticulum stress orchestrates a protective IgA response
Epithelial endoplasmic reticulum stress orchestrates a protective IgA response
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DOI：
10.1126/science.aat7186
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发表时间：
2019-03-01
期刊：
影响因子：
56.9
通讯作者：
Blumberg, Richard S.
中科院分区：
文献类型：
--
作者：
Grootjans, Joep;Krupka, Niklas;Blumberg, Richard S.
免疫球蛋白A （IgA）是在粘膜表面发现的主要分泌性免疫球蛋白同型，它调节微生物共生并排除肠道因子接触肠上皮细胞（IECs）。IgA是由T细胞依赖性和非依赖性（TI）途径诱导的。然而，人们对透明国际的监管知之甚少。我们报道IEC内质网（ER）应激诱导多反应性IgA反应，这是对肠道炎症的保护。iecer应激导致TI和微生物依赖的腹膜B1b细胞扩张和激活，最终导致固有层和腔内IgA增加。在自噬缺陷的健康人群中观察到产生iga的浆细胞数量增加，这些人已知表现为IEC ER应激。内质网应激时，IECs向腹膜传递信号，诱导屏障性TI - IgA反应。
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 microbiotaindependent 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.