Identification of IL4 dependent genes involved in reinforcement stage of Th2 differentiation
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE16022 | GEO | 2010/03/30
SECONDARY ACCESSION(S): PRJNA115451
REPOSITORIES: GEO
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Project description:Naïve CD4+ T-helper cells differentiate into Th2 effector cells during asthma and helminth (worm) infection. Here, we report that mice lacking the transcription factor Bcl11b in mature CD4+ T-cells are incapable of mounting an effective Th2 response in asthma and worm infection, with a major reduction of Th2 cytokine secretion and GATA3 expression. We found that Bcl11b exerts its role in Th2 differentiation through several avenues: (1) association with intronic regions at the Gata3 locus, sustaining GATA3 expression; (2) binding to and restricting chromatin accessibility at the Il4 silencer, located at hypersensitivity site (HS) IV; and (3) restricting Runx3 expression by association with a regulatory region 5’ of Runx3. Thus, in the absence of Bcl11b, the reduction in GATA3 levels combined with increased Runx3 levels and activity at Il4 HS IV silencer and consequently diminished IL-4 expression. This results in reduced chromatin opening at the Th2 locus control region (LCR), Il13 and Il5 promoters, subsequently preventing expression of Th2 cytokine genes and Th2 differentiation. Our results establish a novel role for Bcl11b in the regulatory loop critical for licensing the Th2 program in vivo.
2018-05-09 | GSE99598 | GEO
Project description:Naïve CD4+ T-helper cells differentiate into Th2 effector cells during asthma and helminth (worm) infection. Here, we report that mice lacking the transcription factor Bcl11b in mature CD4+ T-cells are incapable of mounting an effective Th2 response in asthma and worm infection, with a major reduction of Th2 cytokine secretion and GATA3 expression. We found that Bcl11b exerts its role in Th2 differentiation through several avenues: (1) association with intronic regions at the Gata3 locus, sustaining GATA3 expression; (2) binding to and restricting chromatin accessibility at the Il4 silencer, located at hypersensitivity site (HS) IV; and (3) restricting Runx3 expression by association with a regulatory region 5’ of Runx3. Thus, in the absence of Bcl11b, the reduction in GATA3 levels combined with increased Runx3 levels and activity at Il4 HS IV silencer and consequently diminished IL-4 expression. This results in reduced chromatin opening at the Th2 locus control region (LCR), Il13 and Il5 promoters, subsequently preventing expression of Th2 cytokine genes and Th2 differentiation. Our results establish a novel role for Bcl11b in the regulatory loop critical for licensing the Th2 program in vivo.
2018-05-09 | GSE99597 | GEO
Project description:Naïve CD4+ T-helper cells differentiate into Th2 effector cells during asthma and helminth (worm) infection. Here, we report that mice lacking the transcription factor Bcl11b in mature CD4+ T-cells are incapable of mounting an effective Th2 response in asthma and worm infection, with a major reduction of Th2 cytokine secretion and GATA3 expression. We found that Bcl11b exerts its role in Th2 differentiation through several avenues: (1) association with intronic regions at the Gata3 locus, sustaining GATA3 expression; (2) binding to and restricting chromatin accessibility at the Il4 silencer, located at hypersensitivity site (HS) IV; and (3) restricting Runx3 expression by association with a regulatory region 5’ of Runx3. Thus, in the absence of Bcl11b, the reduction in GATA3 levels combined with increased Runx3 levels and activity at Il4 HS IV silencer and consequently diminished IL-4 expression. This results in reduced chromatin opening at the Th2 locus control region (LCR), Il13 and Il5 promoters, subsequently preventing expression of Th2 cytokine genes and Th2 differentiation. Our results establish a novel role for Bcl11b in the regulatory loop critical for licensing the Th2 program in vivo.
2018-05-09 | GSE99595 | GEO
Project description:Gene expression of Treg cells that have lost Foxp3 expression and acquired Il4 expression following adoptive transfer into T-cell deficient mice (HpTR-IL-4gfp+), cmpared to conventional Treg cells isolated from H. polygyrus-infected wild-type mice (HpTR) and Th2 cells generated from naïve T cells following adoptive transfer into H. polygyrus-infected T-cell deficient mice (nT-IL-4gfp+). Immunity to intestinal helminth infections requires the rapid activation of T helper 2 (Th2) cells. However, simultaneous expansion of regulatory CD4+Foxp3+ T (Treg) cells impedes protective responses, resulting in chronic infections. The ratio between regulatory and effector T cells can therefore determine the outcome of infection. The re-differentiation of Treg into T helper (Th) cells has been identified in hyper-inflammatory diseases. In this study, we asked whether ex-Treg Th2 cells develop and contribute to type 2 immunity. Using multi-gene reporter and fate-reporter systems we demonstrate that a significant proportion of Th2 cells derive from Foxp3+ cells following Heligmosomoides polygyrus infection and airway allergy. Ex-Foxp3 Th2 cells exhibit characteristic Th2 effector functions and provide immunity to H. polygyrus. Through selective deletion of Il4ra on Foxp3+ cells, we further demonstrate IL-4 is required for the development of ex-Foxp3 Th2 cells. Collectively, our findings indicate that converting Treg cells into Th2 cells could concomitantly enhance Th2 cells and limit Treg-mediated suppression.
2017-05-04 | GSE98518 | GEO
Project description:T helper type 2 (Th2) responses are crucial for defense against infections by helminths and are responsible for the development of allergic reactions that can lead to severe clinical disorders, such as asthma or anaphylaxis, and ultimately to death. The induction of Th2 responses requires a specific activation process, triggered by specialized dendritic cells (DCs), by which naive CD4+ Th0 cells acquire the capacity to produce Th2 cytokines. However, the mechanistic basis of the functional specialization enabling DCs for the initiation of Th2 responses has remained elusive. Here we show that interleukin-4 (IL-4), a cytokine produced by basophils, mast cells and Th2-polarized CD4+ T helper cells, exerting a crucial function during anti-helminths and allergic Th2 responses, has a key role in the licensing/conditioning of DCs for the induction of Th2 responses, by bloking their potential to produce Th1-driving cytokines, such as IL-12, IL-18 and IL-23. Microarray analyses (duplicates) were for two types of comparisons: 1. moDCs stimulated with LPS from Escherichia coli versus C-moDCs non stimulated (control). 2. moDCs stimulated with LPS from Escherichia coli in presence of IL4 versus C-moDCs non stimulated (control).
2014-02-19 | E-GEOD-39862 | biostudies-arrayexpress
Project description:T helper type 2 (Th2) responses are crucial for defense against infections by helminths and are responsible for the development of allergic reactions that can lead to severe clinical disorders, such as asthma or anaphylaxis, and ultimately to death. The induction of Th2 responses requires a specific activation process, triggered by specialized dendritic cells (DCs), by which naive CD4+ Th0 cells acquire the capacity to produce Th2 cytokines. However, the mechanistic basis of the functional specialization enabling DCs for the initiation of Th2 responses has remained elusive. Here we show that interleukin-4 (IL-4), a cytokine produced by basophils, mast cells and Th2-polarized CD4+ T helper cells, exerting a crucial function during anti-helminths and allergic Th2 responses, has a key role in the licensing/conditioning of DCs for the induction of Th2 responses, by bloking their potential to produce Th1-driving cytokines, such as IL-12, IL-18 and IL-23. Microarray analyses (duplicates) were used to compared the transcriptional profile of monocyte-derived dendritic cells (moDCs) cultured with GM-CSF in the absence or presence of interleukin-4: IL4-moDCs versus C-moDCs.
2014-02-19 | E-GEOD-39858 | biostudies-arrayexpress
Project description:CD4+ helper T cells are critical for immunological response. Th2 cells, a subset of CD4+ helper T cells, are responsible for asthma and other immune diseases. We found a Th2 secreted protein, ExtraCellular Matrix protein 1 (ECM1), which is highly induced by classic IL-4 signaling pathway during helper T cells differentiation. We used microarrays to clarify the global programme of gene expression difference underlying fully developed Th2 cells from WT and ECM1 KO mice and identified distinct classes of up and down regulated genes by ECM1. Naïve CD4+ T cells are seperated from WT and ECM1 mice, cultured and harveseted for RNA extraction and hybridization on Affymetrix microarrays.
2010-12-31 | E-GEOD-19707 | biostudies-arrayexpress
Project description:Mouse splenic naïve T cells were activated (with anti-CD3/CD28)and polarized towards the Th2 subtype with IL4 . Cells were collected at different time points during the differentiation and, at day 3 .5,were collected according to number of cell divisions and expression or absence of a specific differentiation marker.
2016-04-01 | E-MTAB-3543 | biostudies-arrayexpress
Project description:CD4+ helper T cells are critical for immunological response. Th2 cells, a subset of CD4+ helper T cells, are responsible for asthma and other immune diseases. We found a Th2 secreted protein, ExtraCellular Matrix protein 1 (ECM1), which is highly induced by classic IL-4 signaling pathway during helper T cells differentiation. We used microarrays to clarify the global programme of gene expression difference underlying fully developed Th2 cells from WT and ECM1 KO mice and identified distinct classes of up and down regulated genes by ECM1.
2010-12-31 | GSE19707 | GEO
Project description:Naïve CD4 T cells differentiate into functionally diverse subsets of T helper (Th) cells. Gene expression profiling has the capacity to pinpoint factors that regulate subset differentiation and function, however obtaining transcriptional profiles of pure populations has been challenging. We performed single cell RNA-Sequencing (scRNA-Seq) of T helper cells from lymph node, lung and airways in a mouse model of asthma. scRNA-Seq resolved transcriptional profiles of naïve CD4 T, Th1, Th2, Treg cells and various activated states including a population responding to type I interferons. A trajectory for Th2 cell differentiation was delineated over time, with Th2 cells acquiring follicular T helper cell characteristics in the lung-draining lymph node before undergoing further modifications in the lung. A feature of airway Th2 cells was their enrichment for genes associated with lipid metabolism and experiments with blockers of key metabolic pathways supported roles for glucose and lipid metabolism in Th2 cell differentiation.
2019-06-20 | GSE131935 | GEO