Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse SKG FR4-CD4+ cells and age-matched BALB/c FR4-CD4+ cells, and between IFN-g-/- CD4+ cells transferred to RAG2-/- mice and IL-6-/- CD4+ T cells transferred to IL-6-/- RAG2-/- mice

ABSTRACT: Th17 cells are enriched by sorting FR4-CD4+ T cells from SKG mice. A large number of Th17 cells also develop spontaneously when CD4+ T cells from IFN-g-deficient (IFN-g-/-) BALB/c mice are transferred to T cell-deficient RAG2-deficient (RAG2-/-) mice and subjected to homeostatic proliferation, whereas they fail to develop in similar transfer of IL-6-deficient (IL-6-/-) CD4+ T cells to IL-6-/- RAG2-/- mice. To explore the functional molecules specifically expressed by Th17 cells, we conducted Gene Microarray analysis between 10-month-old SKG FR4-CD4+ cells and age-matched BALB/c FR4-CD4+ cells, and between IFN-g-/- CD4+ cells transferred to RAG2-/- mice and IL-6-/- CD4+ T cells transferred to IL-6-/- RAG2-/- mice. The analysis revealed that 1,556 and 115 genes were up-regulated in 10-month-old SKG FR4-CD4+ and IFN-g-/- CD4+ T cells after homeostatic proliferation, respectively, with 29 genes shared by the two groups of genes. The 29 genes included those encoding cytokines, chemokines, and their receptors, such as IL-1 receptor type1 (IL-1R1), IL-17, IL-22, IL-21, CCR6, and CCL20. Experiment Overall Design: We conducted Gene Microarray analysis between 10-month-old SKG FR4-CD4+ cells and age-matched BALB/c FR4-CD4+ cells, and between IFN-g-/- CD4+ cells transferred to RAG2-/- mice and IL-6-/- CD4+ T cells transferred to IL-6-/- RAG2-/- mice using GeneChip Mouse Genome 430 2.0 Array (Affymetrix). Each gruop has three replicates.

ORGANISM(S): Mus musculus

SUBMITTER: Shimon Sakaguchi

PROVIDER: E-GEOD-9316 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model.

Hirota Keiji K Yoshitomi Hiroyuki H Hashimoto Motomu M Maeda Shinji S Teradaira Shin S Sugimoto Naoshi N Yamaguchi Tomoyuki T Nomura Takashi T Ito Hiromu H Nakamura Takashi T Sakaguchi Noriko N Sakaguchi Shimon S

The Journal of experimental medicine 20071119 12

This report shows that interleukin (IL) 17-producing T helper type 17 (Th17) cells predominantly express CC chemokine receptor (CCR) 6 in an animal model of rheumatoid arthritis (RA). Th17 cells induced in vivo in normal mice via homeostatic proliferation similarly express CCR6, whereas those inducible in vitro by transforming growth factor beta and IL-6 additionally need IL-1 and neutralization of interferon (IFN) gamma and IL-4 for CCR6 expression. Forced expression of RORgamma t, a key transc ...[more]

PMID: 18025126

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Project description:Carbo2013 - Cytokine driven CD4+ T Cell differentiation and phenotype plasticity CD4+ T cells can differentiate into different phenotypes depending on the cytokine milieu. Here a computational and mathematical model with sixty ordinary differential equations representing a CD4+ T cell differentiating into either Th1, Th2, Th17 or iTreg cells, has been constructed. The model includes cytokines, nuclear receptors and transcription factors that define fate and function of CD4+ T cells. Computational simulations illustrate how a proinflammatory Th17 cell can undergo reprogramming into an anti-inflammatory iTreg phenotype following PPARc activation. This model is described in the article: Systems Modeling of Molecular Mechanisms Controlling Cytokine-driven CD4+ T Cell Differentiation and Phenotype Plasticity. Carbo A, Hontecillas R, Kronsteiner B, Viladomiu M, Pedragosa M, Lu P, Philipson CW, Hoops S, Marathe M, Eubank S, Bisset K, Wendelsdorf K, Jarrah A, Mei Y, Bassaganya-Riera J PLoS Computational Biology [2013, 9(4):e1003027] Abstract: Differentiation of CD4+ T cells into effector or regulatory phenotypes is tightly controlled by the cytokine milieu, complex intracellular signaling networks and numerous transcriptional regulators. We combined experimental approaches and computational modeling to investigate the mechanisms controlling differentiation and plasticity of CD4+ T cells in the gut of mice. Our computational model encompasses the major intracellular pathways involved in CD4+ T cell differentiation into T helper 1 (Th1), Th2, Th17 and induced regulatory T cells (iTreg). Our modeling efforts predicted a critical role for peroxisome proliferator-activated receptor gamma (PPARγ) in modulating plasticity between Th17 and iTreg cells. PPARγ regulates differentiation, activation and cytokine production, thereby controlling the induction of effector and regulatory responses, and is a promising therapeutic target for dysregulated immune responses and inflammation. Our modeling efforts predict that following PPARγ activation, Th17 cells undergo phenotype switch and become iTreg cells. This prediction was validated by results of adoptive transfer studies showing an increase of colonic iTreg and a decrease of Th17 cells in the gut mucosa of mice with colitis following pharmacological activation of PPARγ. Deletion of PPARγ in CD4+ T cells impaired mucosal iTreg and enhanced colitogenic Th17 responses in mice with CD4+ T cell-induced colitis. Thus, for the first time we provide novel molecular evidence in vivo demonstrating that PPARγ in addition to regulating CD4+ T cell differentiation also plays a major role controlling Th17 and iTreg plasticity in the gut mucosa. Author's comment: CD4+ T cell computational model (Version 1.4) Steady state corrected. There was a problem in the internalization of IL-17 in its mathematical function. This model is hosted on BioModels Database and identified by: MODEL1304230001 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Transcription profiling of mouse SKG FR4-CD4+ cells and age-matched BALB/c FR4-CD4+ cells, and between IFN-g-/- CD4+ cells transferred to RAG2-/- mice and IL-6-/- CD4+ T cells transferred to IL-6-/- RAG2-/- mice

Publications

Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model.

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