Cis-regulation of IL-22 gene in type 3 immune cells [ATAC-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE314539 | GEO | 2026/02/02
REPOSITORIES: GEO
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Project description:IL-22 is a signature cytokine of type 3 immune cells which include ILC3s and Th17/22. Despite its critical role in barrier tissue integrity, the field lacks the understanding of cis mechanisms regulating IL-22. We took initiative to study and reveal the regulatory mechanisms controlling IL-22 expression in ILC3s and Th17/22 cells.
2026-02-02 | GSE314532 | GEO
Project description:IL-22 is a signature cytokine of type 3 immune cells which include ILC3s and Th17/22. Despite its critical role in barrier tissue integrity, the field lacks the understanding of cis mechanisms regulating IL-22. We took initiative to study and reveal the regulatory mechanisms controlling IL-22 expression in ILC3s and Th17/22 cells.
2026-02-02 | GSE314572 | GEO
Project description:IL-22 is a signature cytokine of type 3 immune cells which include ILC3s and Th17/22. Despite its critical role in barrier tissue integrity, the field lacks the understanding of cis mechanisms regulating IL-22. We took initiative to study and reveal the regulatory mechanisms controlling IL-22 expression in ILC3s and Th17/22 cells.
2026-02-02 | GSE314555 | GEO
Project description:IL-22 is a signature cytokine of type 3 immune cells which include ILC3s and Th17/22. Despite its critical role in barrier tissue integrity, the field lacks the understanding of cis mechanisms regulating IL-22. We took initiative to study and reveal the regulatory mechanisms controlling IL-22 expression in ILC3s and Th17/22 cells.
2026-02-02 | GSE314554 | GEO
Project description:Group 3 innate lymphoid cells (ILC3s) are RORγT+ lymphocytes that are predominately enriched in mucosal tissues and produce IL-22 and IL-17A. They are the innate counterparts of Th17. While Th17 lymphocytes utilize unique metabolic pathways in their differentiation program, it is unknown whether ILC3s make similar metabolic adaptations. We employed single-cell RNA sequencing and metabolomic profiling of intestinal ILC subsets to identify an enrichment of polyamine biosynthesis in ILC3s, converging on the rate-limiting enzyme ornithine decarboxylase (ODC1). In vitro and in vivo studies demonstrated that exogenous supplementation with the polyamine putrescine or its biosynthetic substrate, ornithine, enhanced ILC3 production of IL-22. Conditional deletion of ODC1 in ILC3s impaired mouse antibacterial defense against C. rodentium infection, which was associated with a decrease in anti-microbial peptide production by the intestinal epithelium. Furthermore, in a model of anti-CD40 colitis, deficiency of ODC1 in ILC3s markedly reduced the production of IL-22 and severity of inflammatory colitis. We conclude that cell-intrinsic polyamine biosynthesis facilitates efficient defense against enteric pathogens as well as augments autoimmune colitis, thus representing an attractive target to modulate ILC3 function in intestinal disease.
2022-10-06 | GSE214152 | GEO
Project description:While the pathogenesis of asthma is mainly orchestrated by antigen-specific Th2 cells and their cytokines, recent findings indicate the involvement of other subsets of helper T cells including Th17 cells. Previous studies have shown that IL-22, one of Th17 cell-related cytokines, plays multiple roles in regulating allergic airway inflammation; however, the mechanism underlying the Il-22-mediated regulation remains unclear. Here, we show that allergic airway inflammation upon intratracheal administration of house dust mite extract (HDM), a representative allergen, were exacerbated in IL-22-deficient mice. To address the molecular mechanisms by which IL-22 inhibits the development of HDM-induced allergic airway inflammation, we next performed an unbiased comprehensive screening of genes induced by IL-22 administration in the lung by RNA-seq analysis.
2017-08-10 | GSE100858 | GEO
Project description:A20, encoded by the TNFAIP3 gene, is a protein linked to Crohn and celiac disease in humans. We show that mice expressing point mutations in A20’s M1-ubiquitin binding zinc-finger 7 (ZF7) domain spontaneously develop proximal enteritis that requires both luminal microbes and T cells. Cellular and transcriptomic profiling reveal expansion of TH17/22 cells and exuberant expression of IL-17A and IL-22 in intestinal lamina propria of A20ZF7 mice. While deletion of IL-17A from A20ZF7 mice exacerbates enteritis, deletion of IL-22 abrogates intestinal epithelial cell hyperproliferation, barrier dysfunction, and alarmin expression. Colonization of adult germ-free mice with normal luminal flora drives duodenal IL-22 expression and duodenitis. A20ZF7 TH17/22 cells autonomously express more RORgammat and IL-22 after differentiation in vitro. ATAC sequencing identified an enhancer region upstream of the Il22 gene, and this enhancer demonstrated increased activating histone acetylation coupled with exaggerated Il22 transcription in A20ZF7 T cells. Acute inhibition of RORgammat normalized histone acetylation at this enhancer. Finally, CRISPR/Cas9-mediated ablation of A20ZF7 in human T cells increases RORgammat expression and IL22 transcription. These studies link A20’s M1-ubiquitin binding function with RORgammat expression, expansion of TH17/22 cells, and epigenetic activation of IL-22 driven enteritis.
2025-06-12 | GSE296203 | GEO
Project description:A20, encoded by the TNFAIP3 gene, is a protein linked to Crohn and celiac disease in humans. We show that mice expressing point mutations in A20’s M1-ubiquitin binding zinc-finger 7 (ZF7) domain spontaneously develop proximal enteritis that requires both luminal microbes and T cells. Cellular and transcriptomic profiling reveal expansion of TH17/22 cells and exuberant expression of IL-17A and IL-22 in intestinal lamina propria of A20ZF7 mice. While deletion of IL-17A from A20ZF7 mice exacerbates enteritis, deletion of IL-22 abrogates intestinal epithelial cell hyperproliferation, barrier dysfunction, and alarmin expression. Colonization of adult germ-free mice with normal luminal flora drives duodenal IL-22 expression and duodenitis. A20ZF7 TH17/22 cells autonomously express more RORgammat and IL-22 after differentiation in vitro. ATAC sequencing identified an enhancer region upstream of the Il22 gene, and this enhancer demonstrated increased activating histone acetylation coupled with exaggerated Il22 transcription in A20ZF7 T cells. Acute inhibition of RORgammat normalized histone acetylation at this enhancer. Finally, CRISPR/Cas9-mediated ablation of A20ZF7 in human T cells increases RORgammat expression and IL22 transcription. These studies link A20’s M1-ubiquitin binding function with RORgammat expression, expansion of TH17/22 cells, and epigenetic activation of IL-22 driven enteritis.
2025-06-12 | GSE296201 | GEO
Project description:A20, encoded by the TNFAIP3 gene, is a protein linked to Crohn and celiac disease in humans. We show that mice expressing point mutations in A20’s M1-ubiquitin binding zinc-finger 7 (ZF7) domain spontaneously develop proximal enteritis that requires both luminal microbes and T cells. Cellular and transcriptomic profiling reveal expansion of TH17/22 cells and exuberant expression of IL-17A and IL-22 in intestinal lamina propria of A20ZF7 mice. While deletion of IL-17A from A20ZF7 mice exacerbates enteritis, deletion of IL-22 abrogates intestinal epithelial cell hyperproliferation, barrier dysfunction, and alarmin expression. Colonization of adult germ-free mice with normal luminal flora drives duodenal IL-22 expression and duodenitis. A20ZF7 TH17/22 cells autonomously express more RORgammat and IL-22 after differentiation in vitro. ATAC sequencing identified an enhancer region upstream of the Il22 gene, and this enhancer demonstrated increased activating histone acetylation coupled with exaggerated Il22 transcription in A20ZF7 T cells. Acute inhibition of RORgammat normalized histone acetylation at this enhancer. Finally, CRISPR/Cas9-mediated ablation of A20ZF7 in human T cells increases RORgammat expression and IL22 transcription. These studies link A20’s M1-ubiquitin binding function with RORgammat expression, expansion of TH17/22 cells, and epigenetic activation of IL-22 driven enteritis.
2025-06-12 | GSE296200 | GEO
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