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Crosstalk with infant derived Th17 cells promotes maturation of intestinal epithelial cells in an enteroid model through IL-22 signaling

ABSTRACT: The use of 3D human intestinal organoid (HIO) models is growing in biomedical research due to their ability to mimic human tissue for studying diseases, developing biomarkers, and testing therapies. However, current models of the infant gut are limited, focusing mostly on necrotizing enterocolitis, leaving gaps in our understanding of healthy infant gut development. Additionally, achieving full differentiation and maturation of secretory cells, especially Paneth cells, remains challenging. Our studies suggest IL-22 can enhance maturation, though its effects on infant enteroids remain unexplored. In this study, infant-derived ileal enteroids were cultured with Th17 supernatant or IL-22, and their development was assessed via immunofluorescence staining and RNA sequencing. Our results showed that neonatal Th17 cell-derived IL-22 supported the growth and maturation of infant enteroids, including Paneth cell differentiation. IL-22 induced gene expression changes related to cellular identity, maturation, immune response, and barrier function, as revealed by RNAseq analysis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE282290 | GEO | 2025/05/22

REPOSITORIES: GEO

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Crosstalk with infant derived Th17 cells promotes maturation of intestinal epithelial cells in an enteroid model through IL-22 signaling

Project description:Crosstalk with infant derived Th17 cells promotes maturation of intestinal epithelial cells in an enteroid model through IL-22 signaling

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2024-07-01 | GSE248348 | GEO

Type 1 Diabetes Human Enteroid Studies Reveal Major Changes In The Intestinal Epithelial Compartment

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2025-04-16 | GSE264102 | GEO

G-Protein-Coupled Receptor 68 Negatively Regulates IL-22 Production in Human Th17 Cells

Project description:Purpose: To identify novel genes regulated by the aryl hydrocarbon receptor that influence human Th17 cell function. Methods: Naïve CD4 T cells from peripheral blood of six healthy human volunteers were cultured under four experimental conditions for three days: anti-CD3 and anti-CD28 antibodies (Media control), Media with Th17 conditions (IL-6, TGF-b, IL-1b, IL-23), Th17+FICZ and Th17+CH223191. Total RNA was extracted from each sample on day 3 and sequenced in a paired-end 2x50bp strategy on an Illumina HiSeq1500. A total of six donors were analyzed. Results: AhR activation with FICZ suppressed IL-17 production from human CD4 T cells and increased IL-22. AhR inhibition with CH223191 potently suppressed IL-22 and modestly increased IL-17 production. On day 3, the number of significantly regulated genes for each treatment were 975 (Th17), 88 (Th17+FICZ) and 142 (Th17+CH223191). 11 common genes were significantly regulated by all three treatments. One of these, GPR68, was investigated further in functional studies since its expression correlated with IL-22 production. Activation of GPR68 with a positive allosteric modulator suppressed IL-22 concentrations in human Th17 cell cultures. Conclusions: Our study demonstrates that GPR68 activation can negatively regulate IL-22 production from human CD4 T cells in the presence of an AhR agonist. RNA-seq is a powerful method to identify novel gene targets that regulate cytokines involved in chronic inflammatory diseases.

2018-07-19 | GSE102045 | GEO

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