Epithelial endoplasmic reticulum stress orchestrates a protective IgA response

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. PalmMarcel 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

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

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.

Original languageEnglish
Pages (from-to)993-998
Number of pages6
JournalScience
Volume363
Issue number6430
DOIs
StatePublished - 2019
Externally publishedYes

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