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R-spondin driven NF-κB signaling shapes the gastric gland base cell compartment and enables rapid inflammation upon infection of stem cells

ABSTRACT: Mechanisms by which mucosal surfaces discriminate between harmless bacteria and pathogens are not well understood. Gastric gland base colonization by Helicobacter pylori, in contrast to surface colonization causes inflammation and gastric pathology. This compartment contains stem cells, that are controlled by stromal R-spondin 3. Here, we asked how R-spondin 3 and its receptors Lgr4 and Lgr5 control inflammatory responses to H. pylori. We find that epithelial responses to infection are mediated by Rspodnin 3 mainly via Lgr4, causing NF-κB signaling and pro-inflammatory chemokine production. R-spondin 3 signaling induces a baseline NF-κB activity exclusively in the gland base, enabling rapid nuclear translocation of p65 upon infection, triggering inflammtion. Intriguingly, knockout mice that lack NF-κB signaling display an almost complete loss of gland base cells. Our data reveal that gland base cells are primed to act as central proinflammatory mediators, enabling rapid and selective mucosal responses to infections.

ORGANISM(S): Mus musculus

PROVIDER: GSE165028 | GEO | 2022/05/13

REPOSITORIES: GEO

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R-spondin driven NF-κB signaling shapes the gastric gland base cell compartment and enables rapid inflammation upon infection of stem cells

Project description:R-spondin driven NF-κB signaling shapes the gastric gland base cell compartment and enables rapid inflammation upon infection of stem cells

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