TY - JOUR
T1 - Epithelial endoplasmic reticulum stress orchestrates a protective IgA response
AU - Grootjans, Joep
AU - Krupka, Niklas
AU - Hosomi, Shuhei
AU - Matute, Juan D.
AU - Hanley, Thomas
AU - Saveljeva, Svetlana
AU - Gensollen, Thomas
AU - Heijmans, Jarom
AU - Li, Hai
AU - Limenitakis, Julien P.
AU - Ganal-Vonarburg, Stephanie C.
AU - Suo, Shengbao
AU - Luoma, Adrienne M.
AU - Shimodaira, Yosuke
AU - Duan, Jinzhi
AU - Shih, David Q.
AU - Conner, Margaret E.
AU - Glickman, Jonathan N.
AU - Fuhler, Gwenny M.
AU - Palm, Noah W.
AU - de Zoete, Marcel R.
AU - van der Woude, C. Janneke
AU - Yuan, Guo-Cheng
AU - Wucherpfennig, Kai W.
AU - Targan, Stephan R.
AU - Rosenstiel, Philip
AU - Flavell, Richard A.
AU - McCoy, Kathy D.
AU - Macpherson, Andrew J.
AU - Kaser, Arthur
AU - Blumberg, Richard S.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85062394869&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30819965
U2 - https://doi.org/10.1126/science.aat7186
DO - https://doi.org/10.1126/science.aat7186
M3 - Article
C2 - 30819965
SN - 0036-8075
VL - 363
SP - 993
EP - 998
JO - Science
JF - Science
IS - 6430
ER -