Epithelial endoplasmic reticulum stress orchestrates a protective IgA response

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,...

Full description

Saved in:
Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2019-03, Vol.363 (6430), p.993-998
Main Authors: 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
Format: Article
Language:English
Subjects:
Autophagy
Commensalism
Endoplasmic reticulum
Epithelial cells
Epithelium
Gastrointestinal tract
Immunoglobulin A
Immunoglobulins
Lamina propria
Lymphocytes
Lymphocytes T
Microbiota
Microorganisms
Mucosa
Peritoneum
Phagocytosis
Plasma cells
Stress
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0036-8075
1095-9203
1095-9203
DOI:10.1126/science.aat7186