Interleukin 13 Promotes Maturation and Proliferation in Metaplastic Gastroids.
Cell Mol Gastroenterol Hepatol
; 18(3): 101366, 2024.
Article
in En
| MEDLINE
| ID: mdl-38815928
ABSTRACT
BACKGROUND & AIMS:
Type 2 innate lymphoid cells (ILC2s) and interleukin-13 (IL-13) promote the onset of spasmolytic polypeptide-expressing metaplasia (SPEM) cells. However, little is known about molecular effects of IL-13 in SPEM cells. We now sought to establish a reliable organoid model, Meta1 gastroids, to model SPEM cells in vitro. We evaluated cellular and molecular effects of ILC2s and IL-13 on maturation and proliferation of SPEM cells.METHODS:
We performed single-cell RNA sequencing to characterize Meta1 gastroids, which were derived from stomachs of Mist1-Kras transgenic mice that displayed pyloric metaplasia. Cell sorting was used to isolate activated ILC2s from stomachs of IL-13-tdTomato reporter mice treated with L635. Three-dimensional co-culture was used to determine the effects of ILC2s on Meta1 gastroids. Mouse normal or metaplastic (Meta1) and human metaplastic gastroids were cultured with IL-13 to evaluate cell responses. Air-Liquid Interface culture was performed to test long-term culture effects of IL-13. In silico analysis determined possible STAT6-binding sites in gene promoter regions. STAT6 inhibition was performed to corroborate STAT6 role in SPEM cells maturation.RESULTS:
Meta1 gastroids showed the characteristics of SPEM cell lineages in vitro even after several passages. We demonstrated that co-culture with ILC2s or IL-13 treatment can induce phosphorylation of STAT6 in Meta1 and normal gastroids and promote the maturation and proliferation of SPEM cell lineages. IL-13 up-regulated expression of mucin-related proteins in human metaplastic gastroids. Inhibition of STAT6 blocked SPEM-related gene expression in Meta1 gastroids and maturation of SPEM in both normal and Meta1 gastroids.CONCLUSIONS:
IL-13 promotes the maturation and proliferation of SPEM cells consistent with gastric mucosal regeneration.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Mice, Transgenic
/
Interleukin-13
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Cell Proliferation
/
STAT6 Transcription Factor
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Metaplasia
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Mol Gastroenterol Hepatol
/
Cell Mol. Gastroenterol. Hepatol
/
Cellular and molecular gastroenterology and hepatology
Year:
2024
Document type:
Article
Country of publication: