Expression data of ILC2 cells from Ets1-deleted and littermate control mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE79742 | GEO | 2016/04/01
SECONDARY ACCESSION(S): PRJNA316876
REPOSITORIES: GEO
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Project description:The ETS1 transcription factor is required for the development and cytokine-induced expansion of ILC2 ILC2 cells isolated from ETS1-deleted or litter mate control mice were cultured on OP9-DL1 with IL-7 and IL-33. Subsequently, RNA from ICOS+ cells was extracted, labelled and hybridized to Affymetrix microarrays. The goal of this study is to investigate ETS1-dependent genes in developing ILC2 cells.
2016-04-01 | E-GEOD-79742 | biostudies-arrayexpress
Project description:Group 2 innate lymphoid cells (ILC2) are functionally poised, tissue-resident lymphocytes that respond rapidly to damage and infection at mucosal barrier sites. ILC2 reside within complex microenvironments where they are subject to cues from both the diet and invading pathogens – including helminths. Emerging evidence suggests ILC2 are acutely sensitive not only to canonical activating signals, but also perturbations in nutrient availability. In the context of helminth infection, we identify amino acid availability as a nutritional cue in regulating ILC2 responses. ILC2 were found to be uniquely pre-primed to import amino acids via the large neutral amino acid transporters Slc7a5 and Slc7a8. Cell-intrinsic deletion of these transporters individually impaired ILC2 expansion, while concurrent loss of both transporters markedly impaired the proliferative and cytokine producing capacity of ILC2. Moreover, amino acid determined the magnitude of ILC2 responses in part via tuning of mTOR. These findings implicate essential amino acids as a metabolic requisite for optimal ILC2 responses within mucosal barrier tissues.
2022-12-22 | PXD038792 | Pride
Project description:Group 2 innate lymphoid cells (ILC2) are functionally poised, tissue-resident lymphocytes that respond rapidly to damage and infection at mucosal barrier sites. ILC2 reside within complex microenvironments where they are subject to cues from both the diet and invading pathogens – including helminths. Emerging evidence suggests ILC2 are acutely sensitive not only to canonical activating signals, but also perturbations in nutrient availability. In the context of helminth infection, we identify amino acid availability as a nutritional cue in regulating ILC2 responses. ILC2 were found to be uniquely pre-primed to import amino acids via the large neutral amino acid transporters Slc7a5 and Slc7a8. Cell-intrinsic deletion of these transporters individually impaired ILC2 expansion, while concurrent loss of both transporters markedly impaired the proliferative and cytokine producing capacity of ILC2. Moreover, amino acid determined the magnitude of ILC2 responses in part via tuning of mTOR. These findings implicate essential amino acids as a metabolic requisite for optimal ILC2 responses within mucosal barrier tissues.
2022-12-22 | PXD038786 | Pride
Project description:ILC2 cells are a newly described cell type whose biology and contribution to disease are poorly understood. ILC2 cells are activated by allergens, viral infection, and/or epithelial damage via IL-33 and IL-25. ILC2 cells require IL-2, IL-7, IL-25 and IL-33 for their survival and expansion. In mice, ILC2s produce multiple mediators primarily associated with type 2 inflammation (IL-13, IL-5, IL-4, IL-6, IL-9, IL-10, GM-CSF, amphiregulin). ILC2 cells may contribute to the pathology of asthma through multiple mediators that include IL-13-independent pathways. Our goal is to compare transcriptional profiles of IL-33- or IL-25-activated ILC2 cells from blood to characterize these cells and to identify marker(s) that can be utilized to detect them in human tissue. ILC2 cells (Lineage negative, CRTH2+, CD161+, CD127+) were purified from human blood of 5 different donors by flow cytometry. The ILC2 yield ranged from 20,000 to 165,000 cells per donor (0.001-0.008% WBC). Purified ILC2s were expanded in vitro in the presence of IL-2, IL-7, IL-33 and IL-25 (each at 50 ng/ml) for 7-10 days. Expanded cells maintained the ILC2 phenotype (Lineage negative, CRTH2+, CD161+, CD127+). The cells were rested for 2 days in the presence of 1 ng/ml IL-2 and IL-7 and then treated in the presence of 1 ng/ml IL-2 and IL-7 with either media control, IL-25 (50 ng/ml), IL-33 (50 ng/ml), and/or TSLP (50 ng/ml) in combination, for 6 or 24 hours. Whole RNA was isolated via the RNeasy kit (Qiagen). Stratagene Universal Human Reference RNA was used as the reference.
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Project description:Natural killer (NK) cells are innate lymphoid cells that play a critical role in the direct immune defense against tumor cells and pathogens, and additionally have important immune regulatory functions by cytokine secretion. Whereas NK cell biology has been extensively studied in mouse models, transcriptional control of human NK cell differentiation is poorly understood. In this study, we generated ETS1-deficient human embryonic stem cell (hESC) clones using the CRISPR/Cas9 technology. In a complementary approach, we generated ETS1 loss-of-function cord blood hematopoietic stem cells (HSCs) by retroviral transduction of the dominant-negative ETS1 p27 isoform. We show that the transcription factor ETS1 is required for human NK cell differentiation. Transcriptome and ChIP analysis reveal that ETS1 directly regulates expression of several NK cell-linked transcription factors. Also, expression of genes involved in cytokine secretion and cytotoxic activity is ETS1-dependent, whereby these effector functions are decreased in residual NK cells developing from ETS1 loss-of-function cord blood hematopoietic stem cells. Our data show that ETS1 is a critical regulator of human NK cell development and function, and provide important insights in the underlying molecular mechanisms.
2020-10-15 | GSE124103 | GEO
Project description:Natural killer (NK) cells are innate lymphoid cells that play a critical role in the direct immune defense against tumor cells and pathogens, and additionally have important immune regulatory functions by cytokine secretion. Whereas NK cell biology has been extensively studied in mouse models, transcriptional control of human NK cell differentiation is poorly understood. In this study, we generated ETS1-deficient human embryonic stem cell (hESC) clones using the CRISPR/Cas9 technology. In a complementary approach, we generated ETS1 loss-of-function cord blood hematopoietic stem cells (HSCs) by retroviral transduction of the dominant-negative ETS1 p27 isoform. We show that the transcription factor ETS1 is required for human NK cell differentiation. Transcriptome and ChIP analysis reveal that ETS1 directly regulates expression of several NK cell-linked transcription factors. Also, expression of genes involved in cytokine secretion and cytotoxic activity is ETS1-dependent, whereby these effector functions are decreased in residual NK cells developing from ETS1 loss-of-function cord blood hematopoietic stem cells. Our data show that ETS1 is a critical regulator of human NK cell development and function, and provide important insights in the underlying molecular mechanisms.
2020-10-15 | GSE105021 | GEO
Project description:Group 2 innate lymphoid cells (ILC2s) mediate type 2 immune responses involved in anti-helminth immunity, allergic inflammation, and metabolic homeostasis. Recently, they have emerged as key players in regulating tumor immunity. The tumor suppressor liver kinase B1 (LKB1) inactivating mutations is associated with a variety of human cancers, but the role of LKB1 in ILC2 function and ILC2-mediated tumor immunity remains unknown. Here, we show that LKB1 is required for mature ILC2 survival. Ablation of LKB1 in ILC2s results in impaired proliferation and a marked decrease in type 2 cytokine production upon activation, accompanied with the expression of exhaustion signature genes and reduced cellular metabolism, which promote the development of lung melanoma metastasis. In addition, LKB1 deficiency leads to a marked increase of programmed cell death protein-1 (PD-1) expression in ILC2s through activation of nuclear factor of activated T cells (NFAT) pathway. Blockade of PD-1 can restore type 2 cytokine production in LKB1-deficient ILC2 and reverse its exhaustion state, leading to enhanced antitumor immune responses in vivo. Together, our results reveal that LKB1 retrains ILC2 exhaustion state to maintain immune homeostasis and their antitumor immunity.
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Project description:Innate lymphoid cells (ILCs) are able to directly respond to alarmin signals and produce an array of effector molecules for immune protection and tissue homeostasis. However, how posttranscriptional machinery in ILCs execute extracellular stimuli towards robust gene expression is yet to understand. Here, we reported a cell type-specific role of N6-methyladenosine (m6A) RNA methylation in ILCs. Inducible deletion of m6A methyltransferase METTL3 had little impact on ILC maintenance in the steady state or cytokine-induced ILC1 or ILC3 activation, but dramatically diminished IL-25-triggered ILC2 response. Specific deletion of Mettl3 in ILC2 significantly attenuated cell expansion, cytokine production, inter-organ migration, and anti-helminth immunity. To investigate the molecular mechanism by which m6A modification regulates ILC2 response, we subjected ILC2 of WT and Mettl3 Klrg1Cre mice to a m6A-tagged mRNA immunoprecipitation sequencing (meRIP-seq) to identify the m6A modified mRNA.
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Project description:We performed microarray analysis of gene expression in WT and Ets1-/- CD4+ CD8+ DP thymocytes. Overall, we find that Ets1-/- thymocytes display gene expression signatures closer to previous stages of thymocyte development (e.g. DN3-4) than WT DP cells, suggesting that while these cells do become DP thymocytes in the absence of Ets1, that the latter is required for the upregulation of later T-cell genes and that its presence is required for the downregulation of genes corresponding to earlier and alternative stages of development.
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