Epithelial endoplasmic reticulum stress orchestrates a protective IgA response
Grootjans, Joep; Krupka, Niklas; Hosomi, Shuhei; Matute, Juan D; Hanley, Thomas; Saveljeva, Svetlana; Gensollen, Thomas; Heijmans, Jarom; Li, Hai; Limenitakis, Julien P; Ganal-Vonarburg, Stephanie C; Suo, Shengbao; Luoma, Adrienne M; Shimodaira, Yosuke; Duan, Jinzhi; Shih, David Q; Conner, Margaret E; Glickman, Jonathan N; Fuhler, Gwenny M; Palm, Noah W; de Zoete, Marcel R; van der Woude, C Janneke; Yuan, Guo-Cheng; Wucherpfennig, Kai W; Targan, Stephan R; Rosenstiel, Philip; Flavell, Richard A; McCoy, Kathy D; Macpherson, Andrew J; Kaser, Arthur; Blumberg, Richard S
(2019) Science, volume 363, issue 6430, pp. 993 - 998
(Article)
Abstract
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
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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.
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Keywords: Taverne
ISSN: 0036-8075
Publisher: American Association for the Advancement of Science
Note: Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
(Peer reviewed)
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