Kogan2013 - A mathematical model for the immunotherapeutic control of the TH1 TH2 imbalance in melanoma
Ontology highlight
ABSTRACT:
SUBMITTER: 
Johannes Meyer
PROVIDER: BIOMD0000000881 | BioModels | 2024-09-02
REPOSITORIES: BioModels
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Project description:Transcriptional analysis of human T cells differentiated in 4 T Helper context ( Th0, Th1, Th2 and Th17) in the presence or not of Interferon alpha We analyzed the transcriptomic profiles of 4 human naives T cells diferentiated in Th0, Th1, Th2 and Th17 in the presence or not of Interferon Alpha. Microarray analyses were performed in 2 time points : 1/ after Day 5 of polarization (= Day5); 2/ after Day 5+ four hours of re-stimulation (=Day 5+ 4H restim) in 3 different donors.
2014-05-29 | E-GEOD-54627 | 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 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 (Th) cells control host defense to pathogens. IL 12R expression is required for Th1, IL-4RM-NM-1 for Th2, and IL-6RM-NM-1/gp130 for Th17 differentiation to allow responsiveness to IL-12, IL-4, and IL-6, respectively. IL-2 via STAT5 controls Th2 differentiation by regulating the Th2 cytokine gene cluster and Il4ra expression. Here we show that IL-2 regulates Th1 differentiation, inducing STAT5-dependent IL-12RM-NM-22 and T-bet expression, with impaired human Th1 differentiation when IL-2 was blocked. Th1 differentiation was also impaired in mouse Il2-/- T cells but restored by IL-12RM-NM-22 expression. Consistent with IL-2M-bM-^@M-^Ys inhibition of Th17 differentiation, IL-2 decreased Il6ra and Il6st/gp130 expression, and Il6st augmented Th17 differentiation even when IL-2 was present. Thus, IL-2 influences T-cell differentiation by modulating cytokine receptor expression to help specify/maintain differentiated states. Genome-wide mapping of STAT1,STAT4,STAT5A,STAT5B binding to their target genes in Th1 or human CD4+ cells was conducted
2011-04-24 | E-GEOD-27158 | biostudies-arrayexpress
Project description:Transcriptional analysis of human T cells differentiated in 4 T Helper context ( Th0, Th1, Th2 and Th17) in the presence or not of Interferon alpha
2014-05-29 | GSE54627 | GEO
Project description:T helper cells (Th) play an important role guarding, regulating and modulating immune responses. The different Th lineages fulfill different tasks in response to infections. The two best defined subtypes are Th1 (involved in cellular immunity) and Th2 (humoral immunity). The cytokine environment after activation determines the differentiation path of a Th cell. We defined a strategy to investigate the differentiation signature of T helper cells with a proteomics approach. Murine primary naïve CD4+ T-cells from spleen were differentiated and activated in vitro. After 3 days of differentiation proteins were analysed. The proteomic profile of the Th1 and Th2 cells will help understand these phenotypes better, which is important in finding therapeutic targets for disease and for the development of effective vaccines.
2019-02-14 | PXD004532 | Pride
Project description:T helper type 1 (Th1) cells play critical roles in viral infection response and autoimmune disease. Recent studies have implicated the imbalance of T helper subtypes is correlated with outcome of COVID-19 infection, however, the underlying mechanism that balancing Th1 cells versus other T helper cells remains unknown. Here, we profiled the heterogeneity and dynamic regulation during in vivo and in vitro Th1 differentiation using scRNA-seq and defined the Th1 unique program using a Th1/Th2 dichotomous differentiation condition. To further validate the functions of defined Th1 regulators, we performed CRISPR screenings for both in vitro as well as in vivo Th1 differentiation. RAMP3 as one of the receptors for neuropeptide CGRP was defined as a novel regulator balancing Th1 and Th2 differentiation and was proved an indispensable role for Th1 response during virus infection. CGRP, RAMP3 and cAMP signaling form a positive feedback loop to enhance Th1 differentiation through activating STAT1. Together, ur work highlights the network between CGRP-mediated neuronal signaling and immune response during virus infection.
2023-12-25 | GSE192728 | GEO
Project description:Special AT-rich binding protein 1 (SATB1) is a global chromatin organizer and a transcription factor induced by interleukin-4 (IL-4) during the early T helper 2 (Th2) cell differentiation. In this study, we investigated the role of SATB1 in T helper cell differentiation by performing ChIP-on-chip analysis of human cord blood CD4+ T cells cultured in Th1 and Th2 conditions. These results were combined with gene expression profiling results from human differentiating Th cells in which expression of SATB1 was downregulated by RNA interference (RNAi).Our results indicate that SATB1 regulates and is bound to sixty genes in primary human CD4+ T cells, including several IL-12 and/or IL-4 regulated factors, suggesting a role in the development or function of Th subtypes. Cross-linked chromatin obtained from human CD4+ T cells isolated from cord blood cultured in Th1 and Th2 conditions for 24 h was immunoprecipitated with anti-SATB1 antibody.
2010-05-16 | E-GEOD-17380 | biostudies-arrayexpress
Project description:This a model from the article:
Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-gamma and interleukin-12.
Schulz EG, Mariani L, Radbruch A, Höfer T.
Immunity.2009;30(5):666-8.
19409816,
Abstract:
Differentiation of naive T lymphocytes into type I T helper (Th1) cells requires interferon-gamma and interleukin-12. It is puzzling that interferon-gamma induces the Th1 transcription factor T-bet, whereas interleukin-12 mediates Th1 cell lineage differentiation. We use mathematical modeling to analyze the expression kinetics of T-bet, interferon-gamma, and the IL-12 receptor beta2 chain (IL-12Rbeta2) during Th1 cell differentiation, in the presence or absence of interleukin-12 or interferon-gamma signaling. We show that interferon-gamma induced initial T-bet expression, whereas IL-12Rbeta2 was repressed by T cell receptor (TCR) signaling. The termination of TCR signaling permitted upregulation of IL-12Rbeta2 by T-bet and interleukin-12 signaling that maintained T-bet expression. This late expression of T-bet, accompanied by the upregulation of the transcription factors Runx3 and Hlx, was required to imprint the Th cell for interferon-gamma re-expression. Thus initial polarization and subsequent imprinting of Th1 cells are mediated by interlinked, sequentially acting positive feedback loops of TCR-interferon-gamma-Stat1-T-bet and interleukin-12-Stat4-T-bet signaling.
The original model was created by:
Edda G. Schulz
schulz@drfz.de
Theoretical Biophysics, Institute of Biology, Humboldt Universität, Invalidenstrasse 42, 10115 Berlin, Germany.
This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2009 The BioModels Team.For more information see the terms of use.To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.
2024-09-02 | BIOMD0000000215 | BioModels
Project description:T helper (Th) cells control host defense to pathogens. IL 12R expression is required for Th1, IL-4Rα for Th2, and IL-6Rα/gp130 for Th17 differentiation to allow responsiveness to IL-12, IL-4, and IL-6, respectively. IL-2 via STAT5 controls Th2 differentiation by regulating the Th2 cytokine gene cluster and Il4ra expression. Here we show that IL-2 regulates Th1 differentiation, inducing STAT5-dependent IL-12Rβ2 and T-bet expression, with impaired human Th1 differentiation when IL-2 was blocked. Th1 differentiation was also impaired in mouse Il2-/- T cells but restored by IL-12Rβ2 expression. Consistent with IL-2’s inhibition of Th17 differentiation, IL-2 decreased Il6ra and Il6st/gp130 expression, and Il6st augmented Th17 differentiation even when IL-2 was present. Thus, IL-2 influences T-cell differentiation by modulating cytokine receptor expression to help specify/maintain differentiated states.
2011-04-24 | GSE27158 | 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 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