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R-spondin-3 induces secretory, antimicrobial Lgr5+ cells in the stomach
- Source :
- Nature Cell Biology. 21:812-823
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Wnt signalling stimulated by binding of R-spondin (Rspo) to Lgr-family members is crucial for gastrointestinal stem cell renewal. Infection of the stomach with Helicobacter pylori stimulates increased secretion of Rspo by myofibroblasts, leading to an increase in proliferation of Wnt-responsive Axin2+Lgr5- stem cells in the isthmus of the gastric gland and finally gastric gland hyperplasia. Basal Lgr5+ cells are also exposed to Rspo3, but their response remains unclear. Here, we demonstrate that-in contrast to its known mitogenic activity-Rspo3 induces differentiation of basal Lgr5+ cells into secretory cells that express and secrete antimicrobial factors, such as intelectin-1, into the lumen. The depletion of Lgr5+ cells or the knockout of Rspo3 in myofibroblasts leads to hypercolonization of the gastric glands with H. pylori, including the stem cell compartment. By contrast, systemic administration or overexpression of Rspo3 in the stroma clears H. pylori from the gastric glands. Thus, the Rspo3-Lgr5 axis simultaneously regulates both antimicrobial defence and mucosal regeneration.
- Subjects :
- 0303 health sciences
biology
Chemistry
Stomach
LGR5
Cell Biology
Helicobacter pylori
Hyperplasia
biology.organism_classification
medicine.disease
Cell biology
03 medical and health sciences
0302 clinical medicine
medicine.anatomical_structure
Stroma
030220 oncology & carcinogenesis
Gastric glands
medicine
Secretion
Stem cell
030304 developmental biology
Subjects
Details
- ISSN :
- 14764679 and 14657392
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Nature Cell Biology
- Accession number :
- edsair.doi...........ff53fbeeffbf0ab44db7ec4ae2f5b77c