Regulation of group 3 innate lymphoid cells by Setd2 [RNAseqILC3]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE182840 | GEO | 2022/02/23
REPOSITORIES: GEO
Similar Datasets
Project description:To determine the molecular regulation of different subsets of ILC3s by Setd2, small intestinal NKp46- ILC3s (Thy1highCD45low NKp46-) and NKp46+ ILC3s (Thy1highCD45low NKp46+) from Setd2-deficient and control mice were subjected to assay for ATAC-seq.
2022-02-23 | GSE182832 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. To determine the molecular regulation of different subsets of ILC3s by Setd2, small intestinal NKp46- ILC3s (Thy1highCD45low NKp46-) and NKp46+ ILC3s (Thy1highCD45low NKp46+) were purified from littermate Rag1-/-;Setd2f/f or Rag1-/-;Rorc-cre;Setd2f/f mice. Cells were subjected to RNA-seq and ATAC-seq analyses.
2022-02-23 | GSE182844 | GEO
Project description:GATA3 is indispensable for the development of all IL-7Rα-expressing innate lymphoid cells (ILCs) and maintenance of type 1 ILCs (ILC1s) and type 2 ILCs (ILC2s). However, the importance of low GATA3 expression in type 3 ILCs (ILC3s) is still elusive. Here, we report that GATA3 regulates homeostasis of ILC3s by controlling IL-7Rα expression. In addition, GATA3 is critical for the development of NKp46+ ILC3 subset partially through regulating the balance between T-bet and RORγt. Genome-wide analyses indicate that while GATA3 positively regulates CCR6+ and NKp46+ ILC3 subset-specific genes in respective lineages, it negatively regulates CCR6+ ILC3-specific genes in NKp46+ ILC3s. Furthermore, GATA3 regulates IL-22 production in both CCR6+ and NKp46+ ILC3s. Thus, low GATA3 expression is critical for the development and function of ILC3 subsets. To identify GATA3 regulated genes in total ILC3s with RNA-Seq; To identify unique genes expressed by CCR6+ ILC3 or NKp46+ ILC3 and GATA3 regulated genes within these two ILC3 subsets with RNA-Seq; To identify GATA3 direct binding sites in ILC3s, ILC2s and Th2 cells with ChIP-Seq.
2015-11-23 | E-GEOD-71198 | biostudies-arrayexpress
Project description:GATA3 is indispensable for the development of all IL-7Rα-expressing innate lymphoid cells (ILCs) and maintenance of type 1 ILCs (ILC1s) and type 2 ILCs (ILC2s). However, the importance of low GATA3 expression in type 3 ILCs (ILC3s) is still elusive. Here, we report that GATA3 regulates homeostasis of ILC3s by controlling IL-7Rα expression. In addition, GATA3 is critical for the development of NKp46+ ILC3 subset partially through regulating the balance between T-bet and RORγt. Genome-wide analyses indicate that while GATA3 positively regulates CCR6+ and NKp46+ ILC3 subset-specific genes in respective lineages, it negatively regulates CCR6+ ILC3-specific genes in NKp46+ ILC3s. Furthermore, GATA3 regulates IL-22 production in both CCR6+ and NKp46+ ILC3s. Thus, low GATA3 expression is critical for the development and function of ILC3 subsets.
2015-11-23 | GSE71198 | GEO
Project description:Ror gamma t-deficient mice lack group 3 Innate Lymphoid Cells (ILC3s) and as a result have increased tissue damage and diminished tissue repair in response to insult. To identify repair programs associated with ILC3 presence the transcriptomes of small intestinal stem cells exposed to damage in the presence or absence of ILC3 were compared. Small intestinal damage was induced in Ror gamma t-deficient Lgr5 reporter mice and littermate controls. Small intestinal epithelial stem cells were purified at days 1 and 4 after damage and subjected to RNA sequencing.
2018-06-29 | E-MTAB-6639 | biostudies-arrayexpress
Project description:Group 3 innate lymphoid cells (ILC3s) are key players in intestinal homeostasis. Endoplasmic reticulum (ER) stress is linked to inflammatory bowel disease (IBD). Herein, we used cell culture, novel mouse models, and human specimens to examine if ER stress in ILC3s impacts IBD pathophysiology. We show that mouse intestinal ILC3s exhibited a 24h-rhythmic expression pattern of the master ER stress response regulator, IRE1α-XBP1. Proinflammatory cytokine IL-23 selectively stimulated IRE1α-XBP1 in mouse ILC3s through mitochondrial reactive oxygen species (mtROS). IRE1α-XBP1 was activated in ILC3s of mice exposed to experimental colitis and in inflamed human IBD specimens. Mice with Ire1α deletion in ILC3s (Ire1αΔRorc) showed reduced expression of ER stress response and cytokine genes including Il22 in ILC3s and were highly vulnerable to infections and colitis. Administration of IL-22 counteracted their colitis susceptibility. In human ILC3s, IRE1 inhibitors suppressed cytokine production, which was upregulated by an IRE1 activator. Moreover, the frequencies of intestinal XBP1s+ ILC3s in Crohn’s disease patients before administration of ustekinumab, an anti-IL-12/IL-23 antibody, positively correlated with response to treatment. We demonstrate that a non-canonical mtROS-IRE1α-XBP1 pathway augments cytokine production by ILC3s and identify XBP1+ ILC3s as a potential biomarker for predicting response to anti-IL-23 therapies in IBD. Group 3 innate lymphoid cells (ILC3s) have recently emerged as important regulators and potential drug targets for IBD. However, the response of ILC3s to environmental stimuli during intestinal inflammation remains elusive. IRE1a-XBP1 serves as the regulatory hub of the unfolded protein response (UPR) that plays a vital role in intestinal inflammation.
2024-05-31 | GSE261091 | GEO
Project description:Group 3 innate lymphoid cells (ILC3s) are crucial for maintaining mucosal homeostasis and regulating inflammatory diseases, but the molecular mechanisms governing their phenotype and function are not fully understood. Here, we showed that ILC3s highly expressed Fcer1g gene, which encodes the antibody Fc-receptor common gamma chain (FcεR1γ). Genetic perturbation of FcεR1γ led to the absence of critical cell membrane receptors NKp46 and CD16 in ILC3s. Alanine scanning mutagenesis identified two residues in FcεR1γ that stabilize its binding partners. FcεR1γ expression in ILC3s was essential for effective protective immunity against bacterial and fungal infections. Mechanistically, FcεR1γ influenced the transcriptional state and proinflammatory cytokine production of ILC3s, relying on the CD16-FcεR1γ signaling pathway. Overall, our findings highlight the significance of FcεR1γ as an adaptor protein that stabilizes cell membrane partners in ILC3s and promotes anti-infection immunity.
2024-06-05 | GSE256409 | GEO
Project description:We performed RNA-Seq analysis of small intestinal lamina propria ILC3s of Rorc.Cre Maf.flox and Maf.flox control mice.
2020-02-11 | GSE143867 | GEO
Project description:Intestinal innate lymphoid cells (ILCs) contribute to the protective immunity and homeostasis of the gut, and the microbiota are critically involved in shaping ILC function. However, the role of the gut microbiota in regulating ILC development and maintenance still remains elusive. Here, we identified opposing effects on ILCs by two Helicobacter species, Helicobacter apodemus and Helicobacter typhlonius, isolated from immunocompromised mice. We demonstrated that the introduction of both Helicobacter species activated ILCs and induced gut inflammation; however, these Helicobacter species negatively regulated RORγt+ Group 3 ILCs (ILC3s), especially T-bet+ ILC3s, and diminished their proliferative capacity. Thus, these findings underscore a previously unknown dichotomous regulation of ILC3s by Helicobacter species, and may serve as a model for further investigations to elucidate the host-microbe interactions that critically sustain the maintenance of intestinal ILC3s.
2019-11-18 | GSE136171 | GEO
Project description:As an important early source of IL-17A and IL-22 in immune responses, type 3 innate lymphoid cells (ILC3s) are critically regulated by the transcription factor retinoic-acid-receptor-related orphan receptor gamma t (RORγt). Previously, we have identified a crucial role of the conserved non-coding sequence 9 (CNS9), located at +5,802 to +7,963 bp of the Rorc gene, in directing T helper 17 differentiation and related autoimmune disease. However, whether cis-acting elements regulate RORγt expression in ILC3s is unknown. Here we show that CNS9 deficiency in mice not only decreases ILC3 signature gene expression and increases ILC1-gene expression features in total ILC3s, but also leads to generation of a distinct CD4+NKp46+ ILC3 population, though the overall numbers and frequencies of RORγt+ ILC3s are not affected. Mechanistically, CNS9 deficiency selectively decreases RORγt expression in ILC3s, which thus alters ILC3 gene expression features and promotes cell-intrinsic generation of CD4+NKp46+ ILC3 subset. Our study thus identifies CNS9 as an essential cis-regulatory element controlling the lineage stability and plasticity of ILC3s through modulating expression levels of RORγt protein.
2023-02-28 | GSE225928 | GEO