![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
12MB |
![[thumbnail of Supplementary Information incl. Source Data]](https://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplementary Information incl. Source Data)
52MB |
| Item Type: | Article |
|---|---|
| Title: | Helicobacter pylori triggers gastric mucosal remodeling toward a fetal-like transcriptional program via stromal IL-1β signaling |
| Creators: |
Beccaceci, Giulia  ORCID: https://orcid.org/0000-0002-6453-3725, Müllerke, Stefanie, Berger, Hilmar ORCID: https://orcid.org/0000-0002-6304-4946, Täger, Christian, Möbius, Ronja ORCID: https://orcid.org/0009-0008-2988-8951, Fischer, Anne-Sophie ORCID: https://orcid.org/0000-0002-2176-1779, Hartl, Kimberly ORCID: https://orcid.org/0000-0002-2965-0512, Wizenty, Jonas ORCID: https://orcid.org/0000-0003-4261-0416, Mollenkopf, Hans-Joachim ORCID: https://orcid.org/0000-0003-1167-4783, Naumann, Michael ORCID: https://orcid.org/0000-0002-8060-2313, Lin, Manqiang ORCID: https://orcid.org/0000-0003-4093-9277 and Sigal, Michael ORCID: https://orcid.org/0000-0003-4772-0761
|
| Abstract: | In the gastrointestinal tract, Wnt and BMP signals control Lgr5(+) stem cell activity during homeostasis, whereas injury elicits an Lgr5-independent, fetal-like regenerative program driven by YAP. Helicobacter pylori (H. pylori) infection activates YAP, but whether fetal-like reprogramming contributes to gastric pathology, and what drives it, has remained unclear. Here we show that H. pylori-induced gland hyperplasia is accompanied by YAP-dependent fetal-like transcriptional response and loss of epithelial BMP signaling. Epithelial BMP inhibition alone is sufficient to induce this program in vivo, through an epithelial–immune–stromal cascade: BMP-deficient epithelial cells secrete chemokines that recruit IL-1β-producing immune cells, and IL-1β drives enrichment of pro-regenerative fibroblasts producing prostaglandin E2. In gastric epithelial–stromal assembloids, IL-1β elicits stromal prostaglandin E2 production and subsequent epithelial YAP activation. Stromal deletion of the IL-1 receptor abrogates H. pylori-driven reprogramming and pathology. These data define a cascade that converts BMP loss into a fetal-like regenerative state and shapes H. pylori-associated gastric disease. |
| Keywords: | Bone Morphogenetic Proteins, Cell Cycle Proteins, Dinoprostone, Epithelial Cells, Fibroblasts, Gastric Mucosa, Genetic Transcription, Helicobacter Infections, Helicobacter pylori, Inbred C57BL Mice, Interleukin-1 Receptors, Interleukin-1beta, Phosphoproteins, Signal Transducing Adaptor Proteins, Signal Transduction, Stromal Cells, YAP-Signaling Proteins, Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 17 |
| Number: | 1 |
| Page Range: | 9510 |
| Date: | 5 September 2026 |
| Official Publication: | https://doi.org/10.1038/s41467-026-77520-1 |
| PubMed: | View item in PubMed |
| Related to: |
Repository Staff Only: item control page
