Epithelial endoplasmic reticulum stress orchestrates a protective IgA response.

Authors:
Joep Grootjans, Niklas Krupka, Shuhei Hosomi, Juan D Matute, Thomas Hanley, Svetlana Saveljeva, Thomas Gensollen, Jarom Heijmans, Hai Li, Julien P Limenitakis, Stephanie C Ganal-Vonarburg, Shengbao Suo, Adrienne M Luoma, Yosuke Shimodaira, Jinzhi Duan, David Q Shih, Margaret E Conner, Jonathan N Glickman, Gwenny M Fuhler, Noah W Palm, Marcel R de Zoete, C Janneke van der Woude, Guo-Cheng Yuan, Kai W Wucherpfennig, Stephan R Targan, Philip Rosenstiel, Richard A Flavell, Kathy D McCoy, Andrew J Macpherson, Arthur Kaser, Richard S Blumberg
Year of publication:
2019
Volume:
363
Issue:
6430
Issn:
0036-8075
Journal title abbreviated:
SCIENCE
Journal title long:
Science : a weekly journal devoted to the advancement of science / American Association for the Advancement of Science
Impact factor:
63.832
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 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.