CD4+ T-cells during Th2 immune responses
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ABSTRACT:
PROVIDER: PRJNA388879 | ENA |
REPOSITORIES: ENA
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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 | GSE99595 | 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 | GSE99598 | GEO
Project description:The immune response to Neisseria gonorrhoeae is poorly understood, but its extensive antigenic variability and resistance to complement are thought to allow it to evade destruction by the host’s immune defenses. We propose that N. gonorrhoeae also avoids inducing protective immune responses in the first place. We previously found that N. gonorrhoeae induces IL-17-dependent innate responses in mice and suppresses Th1/Th2-dependent adaptive responses in murine cells in vitro through the induction of TGF-β. In this study using a murine model of vaginal gonococcal infection, mice treated with anti-TGF-β antibody during primary infection showed accelerated clearance of N. gonorrhoeae with incipient development of Th1 and Th2 responses and diminished Th17 responses in genital tract tissue. Upon secondary reinfection, mice that had been treated with anti-TGF-β during primary infection showed anamnestic recall of both Th1 and Th2 responses, with the development of anti-gonococcal antibodies in serum and secretions, and enhanced resistance to reinfection. In knockout mouse strains defective in Th1 or Th2 responses, accelerated clearance of primary infection due to anti-TGF-β treatment was dependent on Th1 but not Th2 activity, whereas resistance to secondary infection resulting from anti-TGF-β treatment during primary infection was due to both Th1- and Th2-dependent memory responses. We propose that N. gonorrhoeae proactively elicits Th-17-driven innate responses that it can resist, and suppresses Th1/Th2-driven specific adaptive immunity that would protect the host. Blockade of TGF-β reverses this pattern of host immune responsiveness and facilitates the emergence of protective anti-gonococcal immunity. We only did microarray assay for wild-type mice with or without anti-TGF-b treatment. Experiment A: Totally there are three groups: Sham-infected mice without treatment; N.gonorrhoeae-infected with control IgG treatment; N.gonorrhoeae-infected with anti-TGF-β treatment. For each group, two mice were studied. Total RNA from mouse vagina were analysed. Experiment B: Totally there are three groups: Sham-reinfected mice without treatment; N.gonorrhoeae-reinfected with control IgG treatment; N.gonorrhoeae-reinfected with anti-TGF-β treatment. For each group, two mice were studied. Total RNA from mouse vagina were analysed.
2011-03-22 | E-GEOD-28055 | biostudies-arrayexpress
Project description:The immune response to Neisseria gonorrhoeae is poorly understood, but its extensive antigenic variability and resistance to complement are thought to allow it to evade destruction by the host’s immune defenses. We propose that N. gonorrhoeae also avoids inducing protective immune responses in the first place. We previously found that N. gonorrhoeae induces IL-17-dependent innate responses in mice and suppresses Th1/Th2-dependent adaptive responses in murine cells in vitro through the induction of TGF-β. In this study using a murine model of vaginal gonococcal infection, mice treated with anti-TGF-β antibody during primary infection showed accelerated clearance of N. gonorrhoeae with incipient development of Th1 and Th2 responses and diminished Th17 responses in genital tract tissue. Upon secondary reinfection, mice that had been treated with anti-TGF-β during primary infection showed anamnestic recall of both Th1 and Th2 responses, with the development of anti-gonococcal antibodies in serum and secretions, and enhanced resistance to reinfection. In knockout mouse strains defective in Th1 or Th2 responses, accelerated clearance of primary infection due to anti-TGF-β treatment was dependent on Th1 but not Th2 activity, whereas resistance to secondary infection resulting from anti-TGF-β treatment during primary infection was due to both Th1- and Th2-dependent memory responses. We propose that N. gonorrhoeae proactively elicits Th-17-driven innate responses that it can resist, and suppresses Th1/Th2-driven specific adaptive immunity that would protect the host. Blockade of TGF-β reverses this pattern of host immune responsiveness and facilitates the emergence of protective anti-gonococcal immunity.
2011-03-22 | GSE28055 | GEO
Project description:CD4+ T cells are critical components in the human immune system. They produce cytokines to fight against pathogens and abnormal cells and stimulate other cells, such as B cells, macrophages, and neutrophils, to generate an immune response.
T helper 2 (Th2) cells are subtype CD4+ T cells that differentiate from naive CD4+ T cells in a specific cytokine environment. The Th2 cell model consists of 5252 reactions, 3156 metabolites, and 1127 genes. CD4+ T cell models helped identify drug targets and repurposable drugs against autoimmune diseases.
2023-11-27 | MODEL1909260005 | BioModels
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: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.
2014-02-19 | GSE39862 | 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.
2014-02-19 | GSE39858 | GEO