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.; ... (2019). Epithelial endoplasmic reticulum stress orchestrates a protective IgA response. Science, 363(6430), pp. 993-998. American Association for the Advancement of Science 10.1126/science.aat7186

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine

UniBE Contributor:

Krupka, Niklas; Li, Hai; Limenitakis, Julien Periclis Jean; Ganal-Vonarburg, Stephanie and Macpherson, Andrew

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0036-8075

Publisher:

American Association for the Advancement of Science

Language:

English

Submitter:

Niklas Krupka

Date Deposited:

21 Nov 2019 13:38

Last Modified:

21 Nov 2019 13:38

Publisher DOI:

10.1126/science.aat7186

PubMed ID:

30819965

BORIS DOI:

10.7892/boris.135277

URI:

https://boris.unibe.ch/id/eprint/135277

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