Interleukin-22 enhanced the mucosal barrier and inhibited the invasion of Salmonella enterica in human-induced pluripotent stem cell-derived small intestinal epithelial cells

Abstract Human-induced pluripotent stem cell-derived small intestinal epithelial cell (hiPSC-SIEC) monolayers are useful in vitro models for evaluating the gut mucosal barrier; however, their reactivity to cytokines, which are closely related to the regulation of mucosal barrier function, remains un...

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Bibliographic Details
Published in:FEMS microbiology letters 2024-01, Vol.371
Main Authors: Yamazaki, Fuka, Kobayashi, Kyosuke, Mochizuki, Junko, Sashihara, Toshihiro
Format: Article
Language:English
Subjects:
Cytokines - metabolism
Epithelial Cells - microbiology
Humans
Induced Pluripotent Stem Cells - metabolism
Interleukin-22
Intestinal Mucosa - metabolism
Intestinal Mucosa - pathology
Salmonella
Salmonella enterica - metabolism
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Summary:Abstract Human-induced pluripotent stem cell-derived small intestinal epithelial cell (hiPSC-SIEC) monolayers are useful in vitro models for evaluating the gut mucosal barrier; however, their reactivity to cytokines, which are closely related to the regulation of mucosal barrier function, remains unclear. Interleukin (IL)-22 is a cytokine that contributes to regulate the mucosal barrier in the intestinal epithelia. Using microarray and gene set enrichment analysis, we found that hiPSC-SIEC monolayers activate the immune response and enhance the mucosal barrier in response to IL-22. Moreover, hiPSC-SIEC monolayers induced the gene expression of antimicrobials, including the regenerating islet-derived protein 3 family. Furthermore, IL-22 stimulation upregulated Mucin 2 secretion and gene expression of an enzyme that modifies sugar chains, suggesting alteration of the state of the mucus layer of hiPSC-SIEC monolayers. To evaluate its physiological significance, we measured the protective activity against Salmonella enterica subsp. enterica infection in hiPSC-SIEC monolayers and found that prestimulation with IL-22 reduced the number of viable intracellular bacteria. Collectively, these results suggest that hiPSC-SIEC monolayers enhance the mucosal barrier and inhibit infection by pathogenic bacteria in response to IL-22, as previously reported. These results can contribute to the further application of hiPSC-SIECs in evaluating mucosal barriers. Interleukin-22 induces the innate immune responses related to the mucosal barrier and inhibits infection of pathogenic bacteria in human-induced pluripotent stem cell-derived gut model.
ISSN:1574-6968
1574-6968
DOI:10.1093/femsle/fnae006