The Experts below are selected from a list of 1298082 Experts worldwide ranked by ideXlab platform
John J Oshea - One of the best experts on this subject based on the ideXlab platform.
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transcriptional and epigenetic control of t helper Cell specification molecular mechanisms underlying commitment and plasticity
Annual Review of Immunology, 2012Co-Authors: Yuka Kanno, Golnaz Vahedi, Kiyoshi Hirahara, Kentner Singleton, John J OsheaAbstract:T helper Cell differentiation occurs in the context of the extraCellular cytokine milieu evoked by diverse microbes and other pathogenic stimuli along with T Cell receptor stimulation. The culmination of these signals results in specification of T helper lineages, which occurs through the combinatorial action of multiple transcription factors that establish distinctive transcriptomes. In this manner, inducible, but constitutively active, master regulators work in conjunction with factors such as the signal transducer and activator of transcriptions (STATs) that sense the extraCellular environment. The acquisition of a distinctive transcriptome also depends on chromatin modifications that impact key cis elements as well as the changes in global genomic organization. Thus, signal transduction and epigenetics are linked in these processes of differentiation. In this review, recent advances in understanding T helper lineage specification and deciphering the action of transcription factors are summarized with ...
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genomic views of stat function in cd4 t helper Cell differentiation
Nature Reviews Immunology, 2011Co-Authors: John J Oshea, Golnaz Vahedi, Riitta Lahesmaa, Arian Laurence, Yuka KannoAbstract:This Review describes how next-generation sequencing has enriched our knowledge of how STAT proteins regulate cytokine-mediated T helper Cell differentiation through direct DNA binding and by affecting epigenetic modifications.
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discrete roles of stat4 and stat6 transcription factors in tuning epigenetic modifications and transcription during t helper Cell differentiation
Immunity, 2010Co-Authors: Golnaz Vahedi, Hiroaki Takatori, Haydee L Ramos, Hayato Takahashi, Jonathan Liang, Gustavo Gutierrezcruz, Wendy T. Watford, Chongzhi Zang, Weiqun Peng, John J OsheaAbstract:Summary Signal transducer and activator of transcription 4 (STAT4) and STAT6 are key factors in the specification of helper T Cells; however, their direct roles in driving differentiation are not well understood. Using chromatin immunoprecipitation and massive parallel sequencing, we quantitated the full complement of STAT-bound genes, concurrently assessing global STAT-dependent epigenetic modifications and gene transcription by using Cells from cognate STAT-deficient mice. STAT4 and STAT6 each bound over 4000 genes with distinct binding motifs. Both played critical roles in maintaining chromatin configuration and transcription of a core subset of genes through the combination of different epigenetic patterns. Globally, STAT4 had a more dominant role in promoting active epigenetic marks, whereas STAT6 had a more prominent role in antagonizing repressive marks. Clusters of genes negatively regulated by STATs were also identified, highlighting previously unappreciated repressive roles of STATs. Therefore, STAT4 and STAT6 play wide regulatory roles in T helper Cell specification.
Golnaz Vahedi - One of the best experts on this subject based on the ideXlab platform.
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transcriptional and epigenetic control of t helper Cell specification molecular mechanisms underlying commitment and plasticity
Annual Review of Immunology, 2012Co-Authors: Yuka Kanno, Golnaz Vahedi, Kiyoshi Hirahara, Kentner Singleton, John J OsheaAbstract:T helper Cell differentiation occurs in the context of the extraCellular cytokine milieu evoked by diverse microbes and other pathogenic stimuli along with T Cell receptor stimulation. The culmination of these signals results in specification of T helper lineages, which occurs through the combinatorial action of multiple transcription factors that establish distinctive transcriptomes. In this manner, inducible, but constitutively active, master regulators work in conjunction with factors such as the signal transducer and activator of transcriptions (STATs) that sense the extraCellular environment. The acquisition of a distinctive transcriptome also depends on chromatin modifications that impact key cis elements as well as the changes in global genomic organization. Thus, signal transduction and epigenetics are linked in these processes of differentiation. In this review, recent advances in understanding T helper lineage specification and deciphering the action of transcription factors are summarized with ...
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genomic views of stat function in cd4 t helper Cell differentiation
Nature Reviews Immunology, 2011Co-Authors: John J Oshea, Golnaz Vahedi, Riitta Lahesmaa, Arian Laurence, Yuka KannoAbstract:This Review describes how next-generation sequencing has enriched our knowledge of how STAT proteins regulate cytokine-mediated T helper Cell differentiation through direct DNA binding and by affecting epigenetic modifications.
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Genomic views of STAT function in CD4^+ T helper Cell differentiation
Nature Reviews Immunology, 2011Co-Authors: John J. O'shea, Golnaz Vahedi, Riitta Lahesmaa, Arian Laurence, Yuka KannoAbstract:This Review describes how next-generation sequencing has enriched our knowledge of how STAT proteins regulate cytokine-mediated T helper Cell differentiation through direct DNA binding and by affecting epigenetic modifications. Signal transducer and activator of transcription (STAT) proteins have crucial immunoregulatory functions, and are particularly important for T helper Cell differentiation. Chromatin immunoprecipitation followed by next-generation sequencing (ChIP–seq) analysis has mapped the DNA binding sites of transcription factors such as STATs on a genome-wide scale. ChIP–seq technology also allows researchers to gain a genomic view of the histone epigenetic modifications that constitute the 'epigenome'. Genomic approaches enable us to link transcription factor binding with epigenomic modifications and gene expression to comprehensively evaluate the regulation of these activities. Genome-wide association studies have linked STAT genes and STAT-mediated cytokine signalling pathways to multiple immune deficiency and autoimmune disorders. Further applications of next-generation sequencing technologies include mapping of the DNA methylome, nucleosome positioning and DNase I hypersensitive sites, as well as profiling of the transcriptome (using RNA-seq) and microRNAs, underscoring the versatility of this powerful tool. Signal transducer and activator of transcription (STAT) proteins are well known for their essential roles in transmitting cytokine-mediated signals and specifying T helper (T_H) Cell differentiation. Recent technological advances have revealed that STAT proteins have broad and complex roles in gene regulation and epigenetic control, including important roles as functional repressors. However, the challenge of how to link signal transduction, nucleosome biology and gene regulation remains. The relevance of tackling this problem is highlighted by genome-wide association studies that link cytokine signalling and STATs to various autoimmune or immune deficiency disorders. Defining exactly how extrinsic signals control the specification and plasticity of T_H Cells will provide important insights and perhaps therapeutic opportunities in these diseases.
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discrete roles of stat4 and stat6 transcription factors in tuning epigenetic modifications and transcription during t helper Cell differentiation
Immunity, 2010Co-Authors: Golnaz Vahedi, Hiroaki Takatori, Haydee L Ramos, Hayato Takahashi, Jonathan Liang, Gustavo Gutierrezcruz, Wendy T. Watford, Chongzhi Zang, Weiqun Peng, John J OsheaAbstract:Summary Signal transducer and activator of transcription 4 (STAT4) and STAT6 are key factors in the specification of helper T Cells; however, their direct roles in driving differentiation are not well understood. Using chromatin immunoprecipitation and massive parallel sequencing, we quantitated the full complement of STAT-bound genes, concurrently assessing global STAT-dependent epigenetic modifications and gene transcription by using Cells from cognate STAT-deficient mice. STAT4 and STAT6 each bound over 4000 genes with distinct binding motifs. Both played critical roles in maintaining chromatin configuration and transcription of a core subset of genes through the combination of different epigenetic patterns. Globally, STAT4 had a more dominant role in promoting active epigenetic marks, whereas STAT6 had a more prominent role in antagonizing repressive marks. Clusters of genes negatively regulated by STATs were also identified, highlighting previously unappreciated repressive roles of STATs. Therefore, STAT4 and STAT6 play wide regulatory roles in T helper Cell specification.
Yuka Kanno - One of the best experts on this subject based on the ideXlab platform.
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transcriptional and epigenetic control of t helper Cell specification molecular mechanisms underlying commitment and plasticity
Annual Review of Immunology, 2012Co-Authors: Yuka Kanno, Golnaz Vahedi, Kiyoshi Hirahara, Kentner Singleton, John J OsheaAbstract:T helper Cell differentiation occurs in the context of the extraCellular cytokine milieu evoked by diverse microbes and other pathogenic stimuli along with T Cell receptor stimulation. The culmination of these signals results in specification of T helper lineages, which occurs through the combinatorial action of multiple transcription factors that establish distinctive transcriptomes. In this manner, inducible, but constitutively active, master regulators work in conjunction with factors such as the signal transducer and activator of transcriptions (STATs) that sense the extraCellular environment. The acquisition of a distinctive transcriptome also depends on chromatin modifications that impact key cis elements as well as the changes in global genomic organization. Thus, signal transduction and epigenetics are linked in these processes of differentiation. In this review, recent advances in understanding T helper lineage specification and deciphering the action of transcription factors are summarized with ...
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genomic views of stat function in cd4 t helper Cell differentiation
Nature Reviews Immunology, 2011Co-Authors: John J Oshea, Golnaz Vahedi, Riitta Lahesmaa, Arian Laurence, Yuka KannoAbstract:This Review describes how next-generation sequencing has enriched our knowledge of how STAT proteins regulate cytokine-mediated T helper Cell differentiation through direct DNA binding and by affecting epigenetic modifications.
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Genomic views of STAT function in CD4^+ T helper Cell differentiation
Nature Reviews Immunology, 2011Co-Authors: John J. O'shea, Golnaz Vahedi, Riitta Lahesmaa, Arian Laurence, Yuka KannoAbstract:This Review describes how next-generation sequencing has enriched our knowledge of how STAT proteins regulate cytokine-mediated T helper Cell differentiation through direct DNA binding and by affecting epigenetic modifications. Signal transducer and activator of transcription (STAT) proteins have crucial immunoregulatory functions, and are particularly important for T helper Cell differentiation. Chromatin immunoprecipitation followed by next-generation sequencing (ChIP–seq) analysis has mapped the DNA binding sites of transcription factors such as STATs on a genome-wide scale. ChIP–seq technology also allows researchers to gain a genomic view of the histone epigenetic modifications that constitute the 'epigenome'. Genomic approaches enable us to link transcription factor binding with epigenomic modifications and gene expression to comprehensively evaluate the regulation of these activities. Genome-wide association studies have linked STAT genes and STAT-mediated cytokine signalling pathways to multiple immune deficiency and autoimmune disorders. Further applications of next-generation sequencing technologies include mapping of the DNA methylome, nucleosome positioning and DNase I hypersensitive sites, as well as profiling of the transcriptome (using RNA-seq) and microRNAs, underscoring the versatility of this powerful tool. Signal transducer and activator of transcription (STAT) proteins are well known for their essential roles in transmitting cytokine-mediated signals and specifying T helper (T_H) Cell differentiation. Recent technological advances have revealed that STAT proteins have broad and complex roles in gene regulation and epigenetic control, including important roles as functional repressors. However, the challenge of how to link signal transduction, nucleosome biology and gene regulation remains. The relevance of tackling this problem is highlighted by genome-wide association studies that link cytokine signalling and STATs to various autoimmune or immune deficiency disorders. Defining exactly how extrinsic signals control the specification and plasticity of T_H Cells will provide important insights and perhaps therapeutic opportunities in these diseases.
Riitta Lahesmaa - One of the best experts on this subject based on the ideXlab platform.
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Early T helper Cell programming of gene expression in human.
Seminars in Immunology, 2013Co-Authors: Soile Tuomela, Riitta LahesmaaAbstract:Abstract Molecular mechanisms guiding naive T helper Cell differentiation into functionally specified effector Cells are intensively studied. The rapidly growing knowledge is mainly achieved by using mouse Cells or disease models. Comparatively exiguous data is gathered from human primary Cells although they provide the “ultimate model” for immunology in man, have been exploited in many original studies paving the way for the field, and can be analyzed more easily than ever with the help of modern technology and methods. As usage of mouse models is unavoidable in translational research, parallel human and mouse studies should be performed to assure the relevancy of the hypothesis created during the basic research. In this review, we give an overview on the status of the studies conducted with human primary Cells aiming at elucidating the mechanisms instructing the priming of T helper Cell subtypes. The special emphasis is given to the recent high-throughput studies. In addition, by comparing the human and mouse studies we intend to point out the regulatory mechanisms and questions which are lacking examination with human primary Cells.
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From a gene-centric to whole-proteome view of differentiation of T helper Cell subsets
Briefings in Functional Genomics, 2013Co-Authors: Tapio Lönnberg, Zhi Chen, Riitta LahesmaaAbstract:Proper differentiation of naive T helper Cells into functionally distinct subsets is of critical importance to human health. Consequently, the process is tightly controlled by a complex intraCellular signalling network. To dissect the regulatory principles of this network, immunologists have early on embraced system-wide transcriptomics tools, leading to identification of large panels of potential regulatory factors. In contrast, the use of proteomics approaches in T helper Cell research has been notably rare, and to this date relatively few high-throughput datasets have been reported. Here, we discuss the importance of such research and envision the possibilities afforded by mass spectrometry-based proteomics in the near future.
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genomic views of stat function in cd4 t helper Cell differentiation
Nature Reviews Immunology, 2011Co-Authors: John J Oshea, Golnaz Vahedi, Riitta Lahesmaa, Arian Laurence, Yuka KannoAbstract:This Review describes how next-generation sequencing has enriched our knowledge of how STAT proteins regulate cytokine-mediated T helper Cell differentiation through direct DNA binding and by affecting epigenetic modifications.
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Genomic views of STAT function in CD4^+ T helper Cell differentiation
Nature Reviews Immunology, 2011Co-Authors: John J. O'shea, Golnaz Vahedi, Riitta Lahesmaa, Arian Laurence, Yuka KannoAbstract:This Review describes how next-generation sequencing has enriched our knowledge of how STAT proteins regulate cytokine-mediated T helper Cell differentiation through direct DNA binding and by affecting epigenetic modifications. Signal transducer and activator of transcription (STAT) proteins have crucial immunoregulatory functions, and are particularly important for T helper Cell differentiation. Chromatin immunoprecipitation followed by next-generation sequencing (ChIP–seq) analysis has mapped the DNA binding sites of transcription factors such as STATs on a genome-wide scale. ChIP–seq technology also allows researchers to gain a genomic view of the histone epigenetic modifications that constitute the 'epigenome'. Genomic approaches enable us to link transcription factor binding with epigenomic modifications and gene expression to comprehensively evaluate the regulation of these activities. Genome-wide association studies have linked STAT genes and STAT-mediated cytokine signalling pathways to multiple immune deficiency and autoimmune disorders. Further applications of next-generation sequencing technologies include mapping of the DNA methylome, nucleosome positioning and DNase I hypersensitive sites, as well as profiling of the transcriptome (using RNA-seq) and microRNAs, underscoring the versatility of this powerful tool. Signal transducer and activator of transcription (STAT) proteins are well known for their essential roles in transmitting cytokine-mediated signals and specifying T helper (T_H) Cell differentiation. Recent technological advances have revealed that STAT proteins have broad and complex roles in gene regulation and epigenetic control, including important roles as functional repressors. However, the challenge of how to link signal transduction, nucleosome biology and gene regulation remains. The relevance of tackling this problem is highlighted by genome-wide association studies that link cytokine signalling and STATs to various autoimmune or immune deficiency disorders. Defining exactly how extrinsic signals control the specification and plasticity of T_H Cells will provide important insights and perhaps therapeutic opportunities in these diseases.
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An insight into molecular mechanisms of human T helper Cell differentiation.
Annals of Medicine, 2009Co-Authors: Kirsi J. Rautajoki, Minna K. Kyläniemi, Sunil K. Raghav, Riitta LahesmaaAbstract:Selective activation of T helper (Th) Cell subsets plays an important role in immune response to pathogens as well as in the pathogenesis of human allergy and inflammatory diseases. Th1 Cells along with the recently discovered Th17 Cells play a role in the pathogenesis of autoimmune diseases. Th2 cytokines lead to series of inflammatory processes characteristic for asthma and other atopic diseases. To understand the pathogenesis of immune-mediated diseases it is crucial to dissect pathways and regulatory networks leading to the development of distinct Th subsets. Such knowledge may lead to better strategies for developing diagnostics and therapies for these diseases. The differentiation of Th1, Th2, and Th17 effector Cells is driven by signals originating from T Cell and costimulatory receptors as well as cytokines in the surroundings of activated naive T helper Cells. There are several proteins involved in the regulation of this differentiation process. Most of the data on T helper Cell differentiation h...
Vijay K Kuchroo - One of the best experts on this subject based on the ideXlab platform.
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Cytokines and transcription factors in the differentiation of CD4+ T helper Cell subsets and induction of tissue inflammation and autoimmunity.
Current opinion in immunology, 2020Co-Authors: Mathias Pawlak, Vijay K KuchrooAbstract:CD4+T helper (Th) Cells are critical in homeostasis and host defense but are also central to the development of various autoimmune diseases if they become dysregulated. Specifically, pathogenic Th1 and Th17 Cells contribute to autoimmune inflammation whereas Treg and Tr1 Cells are important for maintaining immune tolerance and resolution of inflammation, respectively. Cytokines trigger signaling pathways in naive T Cells that induce lineage-defining transcription factors that direct their differentiation into the distinct T helper Cell subsets. It has become clear that the differentiation of T helper Cells is not only influenced by the cytokine milieu but also by their metabolic state, cues from the microbiota and the tissue they reside in. A comprehensive understanding how these various stimuli contribute to T helper Cell differentiation and phenotype could potentially provide novel ways for therapeutic intervention in autoimmunity and tissue inflammation.
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Role of Co-stimulatory Molecules in T Helper Cell Differentiation.
Advances in experimental medicine and biology, 2019Co-Authors: Michelle Schorer, Vijay K Kuchroo, Nicole JollerAbstract:CD4+ T Cells play a central role in orchestrating the immune response to a variety of pathogens but also regulate autoimmune responses, asthma, allergic responses, as well as tumor immunity. To cover this broad spectrum of responses, naive CD4+ T Cells differentiate into one of several lineages of T helper Cells, including Th1, Th2, Th17, and TFH, as defined by their cytokine pattern and function. The fate decision of T helper Cell differentiation integrates signals delivered through the T Cell receptor, cytokine receptors, and the pattern of co-stimulatory signals received. In this review, we summarize the contribution of co-stimulatory and co-inhibitory receptors to the differentiation and maintenance of T helper Cell responses.
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autopathogenic t helper Cell type 1 th1 and protective th2 clones differ in their recognition of the autoantigenic peptide of myelin proteolipid protein
Journal of Experimental Medicine, 1997Co-Authors: Lindsay B Nicholson, Judith M. Greer, Vijay K KuchrooAbstract:We previously generated a panel of T helper Cell 1 (Th1) clones specific for an encephalitogenic peptide of myelin proteolipid protein (PLP) peptide 139–151 (HSLGKWLGHPDKF) that induces experimental autoimmune encephalomyelitis (EAE) upon adoptive transfer. In spite of the differences in their T Cell receptor (TCR) gene usage, all these Th1 clones required W144 as the primary and most critical TCR contact residue for the activation. In this study, we determined the TCR contact residues of a panel of Th2/Th0 clones specific for the PLP peptide 139–151 generated either by immunization with the PLP 139–151 peptide with anti– B7-1 antibody or by immunization with an altered peptide Q144. Using alanine-substituted peptide analogues of the native PLP peptide, we show that the Th2 clones have shifted their primary contact residue to the NH2-terminal end of the peptide. These Th2 Cells do not show any dependence on the W144, but show a critical requirement for L141/G142 as their major TCR contact residue. Thus, in contrast with the Th1 clones that did not proliferate to A144-substituted peptide, the Th2 clones tolerated a substitution at position 144 and proliferated to A144 peptide. This alternative A144 reactive repertoire appears to have a critical role in the regulation of autoimmune response to PLP 139–151 because preimmunization with A144 to expand the L141/G142-reactive repertoire protects mice from developing EAE induced with the native PLP 139–151 peptide. These data suggest that a balance between two different T Cell repertoires specific for same autoantigenic epitope can determine disease phenotype, i.e., resistance or susceptibility to an autoimmune disease.