Gelsolin regulates intestinal stem cell regeneration and Th17 cellular function.
Animals
Th17 Cells
/ immunology
Gelsolin
/ genetics
Stem Cells
/ metabolism
Regeneration
Mice
Intestines
/ cytology
Mice, Knockout
Mice, Inbred C57BL
Cell Differentiation
Colitis
/ chemically induced
STAT3 Transcription Factor
/ metabolism
Interleukin-17
/ metabolism
Nuclear Receptor Subfamily 1, Group F, Member 3
/ metabolism
Signal Transduction
Organoids
/ metabolism
Intestinal Mucosa
Radiation, Ionizing
Gelsolin (Gelsolin)
IL-17 signaling pathway
IR induced intestinal injury
Intestinal stem cells (ISCs)
T helper cells 17 (Th17 cells)
Journal
Cell communication and signaling : CCS
ISSN: 1478-811X
Titre abrégé: Cell Commun Signal
Pays: England
ID NLM: 101170464
Informations de publication
Date de publication:
29 Oct 2024
29 Oct 2024
Historique:
received:
24
05
2024
accepted:
20
10
2024
medline:
30
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
epublish
Résumé
Intestinal stem cells (ISCs) are responsible for intestinal homeostasis and are important for the regeneration of damaged intestine. We established an ionizing radiation (IR)-induced intestinal injury model and observed that Gelsolin KO mice had increased radiosensitivity. The deletion of Gelsolin aggravated intestinal damage and reduced the number of ISCs after lethal IR. The intestinal organoid experiments showed that Gelsolin deletion inhibited ISCs function after IR. Notably, RNA sequencing and RT-PCR results showed IL-17 signaling pathway was down-regulated and Th17 cells differentiation was inhibited in Gelsolin KO mice. Moreover, recombinant IL-17 A ameliorated IR-induced intestinal injury and promoted ISCs regeneration. To figure out the role of Gelsolin in Th17 cells differentiation, flow cytometry was used and we found that Gelsolin targets Th17 cells functionality via the p-STAT3/RORγt axis. By establishing the co-culture system, we proved that Th17 cells promoted self-renewal and budding abilities in Gelsolin-deficient organoids. Finally, we found that Gelsolin was protective against DSS-induced colitis and that this protective effect was not specific or limited to the IR induced intestinal injury model. Based on these results, we proved Gelsolin maintained the regeneration of ISCs by sustaining Th17 cells functions via the p-STAT3/RORγt axis.
Identifiants
pubmed: 39472865
doi: 10.1186/s12964-024-01902-5
pii: 10.1186/s12964-024-01902-5
doi:
Substances chimiques
Gelsolin
0
STAT3 Transcription Factor
0
Interleukin-17
0
Nuclear Receptor Subfamily 1, Group F, Member 3
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
524Subventions
Organisme : Youth Training Program
ID : No. 21QNPY034
Organisme : National Natural Science Foundation of China
ID : No.81372932
Organisme : National Natural Science Foundation of China
ID : No. 81872559
Informations de copyright
© 2024. The Author(s).
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