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  • 1
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    Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-07-23
    Description: 5-methylcytosine (5mC) in DNA plays an important role in gene expression, genomic imprinting, and suppression of transposable elements. 5mC can be converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) proteins. Here, we show that, in addition to 5hmC, the Tet proteins can generate 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) from 5mC in an enzymatic activity-dependent manner. Furthermore, we reveal the presence of 5fC and 5caC in genomic DNA of mouse embryonic stem cells and mouse organs. The genomic content of 5hmC, 5fC, and 5caC can be increased or reduced through overexpression or depletion of Tet proteins. Thus, we identify two previously unknown cytosine derivatives in genomic DNA as the products of Tet proteins. Our study raises the possibility that DNA demethylation may occur through Tet-catalyzed oxidation followed by decarboxylation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3495246/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3495246/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ito, Shinsuke -- Shen, Li -- Dai, Qing -- Wu, Susan C -- Collins, Leonard B -- Swenberg, James A -- He, Chuan -- Zhang, Yi -- GM071440/GM/NIGMS NIH HHS/ -- GM68804/GM/NIGMS NIH HHS/ -- P30 ES010126/ES/NIEHS NIH HHS/ -- P30 ES010126-11/ES/NIEHS NIH HHS/ -- P30ES10126/ES/NIEHS NIH HHS/ -- P42 ES005948/ES/NIEHS NIH HHS/ -- P42 ES005948-17/ES/NIEHS NIH HHS/ -- P42ES5948/ES/NIEHS NIH HHS/ -- R01 GM068804/GM/NIGMS NIH HHS/ -- U01 DK089565/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Sep 2;333(6047):1300-3. doi: 10.1126/science.1210597. Epub 2011 Jul 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21778364" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/*metabolism ; Animals ; Cell Line ; Cytosine/*analogs & derivatives/metabolism ; DNA/*metabolism ; DNA Methylation ; DNA-Binding Proteins/genetics/*metabolism ; Embryonic Stem Cells/metabolism ; Humans ; Mice ; Oxidation-Reduction ; Proto-Oncogene Proteins/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Global epigenomic reconfiguration during mammalian brain development (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-07-06
    Description: DNA methylation is implicated in mammalian brain development and plasticity underlying learning and memory. We report the genome-wide composition, patterning, cell specificity, and dynamics of DNA methylation at single-base resolution in human and mouse frontal cortex throughout their lifespan. Widespread methylome reconfiguration occurs during fetal to young adult development, coincident with synaptogenesis. During this period, highly conserved non-CG methylation (mCH) accumulates in neurons, but not glia, to become the dominant form of methylation in the human neuronal genome. Moreover, we found an mCH signature that identifies genes escaping X-chromosome inactivation. Last, whole-genome single-base resolution 5-hydroxymethylcytosine (hmC) maps revealed that hmC marks fetal brain cell genomes at putative regulatory regions that are CG-demethylated and activated in the adult brain and that CG demethylation at these hmC-poised loci depends on Tet2 activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785061/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785061/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lister, Ryan -- Mukamel, Eran A -- Nery, Joseph R -- Urich, Mark -- Puddifoot, Clare A -- Johnson, Nicholas D -- Lucero, Jacinta -- Huang, Yun -- Dwork, Andrew J -- Schultz, Matthew D -- Yu, Miao -- Tonti-Filippini, Julian -- Heyn, Holger -- Hu, Shijun -- Wu, Joseph C -- Rao, Anjana -- Esteller, Manel -- He, Chuan -- Haghighi, Fatemeh G -- Sejnowski, Terrence J -- Behrens, M Margarita -- Ecker, Joseph R -- AI44432/AI/NIAID NIH HHS/ -- CA151535/CA/NCI NIH HHS/ -- HD065812/HD/NICHD NIH HHS/ -- HG006827/HG/NHGRI NIH HHS/ -- K99NS080911/NS/NINDS NIH HHS/ -- MH094670/MH/NIMH NIH HHS/ -- R01 AI044432/AI/NIAID NIH HHS/ -- R01 CA151535/CA/NCI NIH HHS/ -- R01 HD065812/HD/NICHD NIH HHS/ -- R01 HG006827/HG/NHGRI NIH HHS/ -- R01 MH094670/MH/NIMH NIH HHS/ -- R01 MH094774/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Aug 9;341(6146):1237905. doi: 10.1126/science.1237905. Epub 2013 Jul 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. ryan.lister@uwa.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23828890" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/metabolism ; Adult ; Animals ; Base Sequence ; Conserved Sequence ; Cytosine/*analogs & derivatives/metabolism ; *DNA Methylation ; *Epigenesis, Genetic ; Epigenomics ; Frontal Lobe/*growth & development ; *Gene Expression Regulation, Developmental ; Genome-Wide Association Study ; Humans ; Longevity ; Mice ; Mice, Inbred C57BL ; X Chromosome Inactivation/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    Dynamic regulatory network controlling TH17 cell differentiation (2013)
    Nature Publishing Group (NPG)
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    Publication Date: 2013-03-08
    Description: Despite their importance, the molecular circuits that control the differentiation of naive T cells remain largely unknown. Recent studies that reconstructed regulatory networks in mammalian cells have focused on short-term responses and relied on perturbation-based approaches that cannot be readily applied to primary T cells. Here we combine transcriptional profiling at high temporal resolution, novel computational algorithms, and innovative nanowire-based perturbation tools to systematically derive and experimentally validate a model of the dynamic regulatory network that controls the differentiation of mouse TH17 cells, a proinflammatory T-cell subset that has been implicated in the pathogenesis of multiple autoimmune diseases. The TH17 transcriptional network consists of two self-reinforcing, but mutually antagonistic, modules, with 12 novel regulators, the coupled action of which may be essential for maintaining the balance between TH17 and other CD4(+) T-cell subsets. Our study identifies and validates 39 regulatory factors, embeds them within a comprehensive temporal network and reveals its organizational principles; it also highlights novel drug targets for controlling TH17 cell differentiation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637864/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637864/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yosef, Nir -- Shalek, Alex K -- Gaublomme, Jellert T -- Jin, Hulin -- Lee, Youjin -- Awasthi, Amit -- Wu, Chuan -- Karwacz, Katarzyna -- Xiao, Sheng -- Jorgolli, Marsela -- Gennert, David -- Satija, Rahul -- Shakya, Arvind -- Lu, Diana Y -- Trombetta, John J -- Pillai, Meenu R -- Ratcliffe, Peter J -- Coleman, Mathew L -- Bix, Mark -- Tantin, Dean -- Park, Hongkun -- Kuchroo, Vijay K -- Regev, Aviv -- 1P50HG006193-01/HG/NHGRI NIH HHS/ -- 5DP1OD003893-03/OD/NIH HHS/ -- AI073748/AI/NIAID NIH HHS/ -- AI45757/AI/NIAID NIH HHS/ -- DP1 OD003893/OD/NIH HHS/ -- DP1 OD003958/OD/NIH HHS/ -- DP1OD003958-01/OD/NIH HHS/ -- F32 HD075541/HD/NICHD NIH HHS/ -- K01 DK090105/DK/NIDDK NIH HHS/ -- NS 30843/NS/NINDS NIH HHS/ -- NS045937/NS/NINDS NIH HHS/ -- P01 AI045757/AI/NIAID NIH HHS/ -- P01 AI073748/AI/NIAID NIH HHS/ -- P50 HG006193/HG/NHGRI NIH HHS/ -- R01 AI100873/AI/NIAID NIH HHS/ -- R01 NS030843/NS/NINDS NIH HHS/ -- R01 NS045937/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Apr 25;496(7446):461-8. doi: 10.1038/nature11981. Epub 2013 Mar 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23467089" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD95/metabolism ; Cell Differentiation/*genetics ; Cells, Cultured ; DNA/genetics/metabolism ; Forkhead Transcription Factors/metabolism ; Gene Knockdown Techniques ; Gene Regulatory Networks/*genetics ; Genome/genetics ; Interferon-gamma/biosynthesis ; Interleukin-2/genetics ; Mice ; Mice, Inbred C57BL ; Nanowires ; Neoplasm Proteins/metabolism ; Nuclear Proteins/metabolism ; RNA, Messenger/genetics/metabolism ; Reproducibility of Results ; Silicon ; Th17 Cells/*cytology/immunology/*metabolism ; Time Factors ; Trans-Activators/metabolism ; Transcription Factors/metabolism ; Transcription, Genetic/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
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    Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-11-13
    Description: Diagnosis of pancreatic ductal adenocarcinoma (PDAC) is associated with a dismal prognosis despite current best therapies; therefore new treatment strategies are urgently required. Numerous studies have suggested that epithelial-to-mesenchymal transition (EMT) contributes to early-stage dissemination of cancer cells and is pivotal for invasion and metastasis of PDAC. EMT is associated with phenotypic conversion of epithelial cells into mesenchymal-like cells in cell culture conditions, although such defined mesenchymal conversion (with spindle-shaped morphology) of epithelial cells in vivo is rare, with quasi-mesenchymal phenotypes occasionally observed in the tumour (partial EMT). Most studies exploring the functional role of EMT in tumours have depended on cell-culture-induced loss-of-function and gain-of-function experiments involving EMT-inducing transcription factors such as Twist, Snail and Zeb1 (refs 2, 3, 7-10). Therefore, the functional contribution of EMT to invasion and metastasis remains unclear, and genetically engineered mouse models to address a causal connection are lacking. Here we functionally probe the role of EMT in PDAC by generating mouse models of PDAC with deletion of Snail or Twist, two key transcription factors responsible for EMT. EMT suppression in the primary tumour does not alter the emergence of invasive PDAC, systemic dissemination or metastasis. Suppression of EMT leads to an increase in cancer cell proliferation with enhanced expression of nucleoside transporters in tumours, contributing to enhanced sensitivity to gemcitabine treatment and increased overall survival of mice. Collectively, our study suggests that Snail- or Twist-induced EMT is not rate-limiting for invasion and metastasis, but highlights the importance of combining EMT inhibition with chemotherapy for the treatment of pancreatic cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zheng, Xiaofeng -- Carstens, Julienne L -- Kim, Jiha -- Scheible, Matthew -- Kaye, Judith -- Sugimoto, Hikaru -- Wu, Chia-Chin -- LeBleu, Valerie S -- Kalluri, Raghu -- P30 CA016672/CA/NCI NIH HHS/ -- P30CA16672/CA/NCI NIH HHS/ -- England -- Nature. 2015 Nov 26;527(7579):525-30. doi: 10.1038/nature16064. Epub 2015 Nov 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA. ; Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA. ; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. ; Department of Bioengineering, Rice University, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26560028" target="_blank"〉PubMed〈/a〉
    Keywords: Adenocarcinoma/drug therapy/metabolism/pathology ; Animals ; Carcinoma, Pancreatic Ductal/drug therapy/metabolism/pathology ; Cell Proliferation/drug effects ; Deoxycytidine/analogs & derivatives/pharmacology/therapeutic use ; Disease Models, Animal ; Disease Progression ; Drug Resistance, Neoplasm/*drug effects ; *Epithelial-Mesenchymal Transition ; Female ; Male ; Mice ; Neoplasm Invasiveness/pathology ; Neoplasm Metastasis/*pathology ; Nucleoside Transport Proteins/metabolism ; Pancreatic Neoplasms/*drug therapy/genetics/metabolism/*pathology ; Survival Analysis ; Transcription Factors/deficiency/genetics/metabolism ; Twist Transcription Factor/deficiency/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 5
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    Lift NIH restrictions on chimera research (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sharma, Arun -- Sebastiano, Vittorio -- Scott, Christopher T -- Magnus, David -- Koyano-Nakagawa, Naoko -- Garry, Daniel J -- Witte, Owen N -- Nakauchi, Hiromitsu -- Wu, Joseph C -- Weissman, Irving L -- Wu, Sean M -- New York, N.Y. -- Science. 2015 Nov 6;350(6261):640. doi: 10.1126/science.350.6261.640-a. Epub 2015 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Center for Biomedical Ethics, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA. ; Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA. Stem Cell Institute and Paul and Sheila Wellstone Muscular Dystrophy Center, University of Minnesota, Minneapolis, MN 55455, USA. Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA. ; Broad Stem Cell Research Center and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. ; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. Center for Stem Cell Biology and Regenerative Medicine, The University of Tokyo, Tokyo, Japan. ; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. irv@stanford.edu smwu@stanford.edu. ; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. irv@stanford.edu smwu@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26542560" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Bioethical Issues ; Blastocyst ; *Chimera ; Financial Management/ethics ; Humans ; Mice ; National Institutes of Health (U.S.)/economics/ethics ; Pluripotent Stem Cells/*transplantation ; Stem Cell Research/economics/*ethics ; United States
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-04-20
    Description: Long noncoding RNAs (lncRNAs) play important roles in diverse biological processes; however, few have been identified that regulate immune cell differentiation and function. Here, we identified lnc-DC, which was exclusively expressed in human conventional dendritic cells (DCs). Knockdown of lnc-DC impaired DC differentiation from human monocytes in vitro and from mouse bone marrow cells in vivo and reduced capacity of DCs to stimulate T cell activation. lnc-DC mediated these effects by activating the transcription factor STAT3 (signal transducer and activator of transcription 3). lnc-DC bound directly to STAT3 in the cytoplasm, which promoted STAT3 phosphorylation on tyrosine-705 by preventing STAT3 binding to and dephosphorylation by SHP1. Our work identifies a lncRNA that regulates DC differentiation and also broadens the known mechanisms of lncRNA action.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Pin -- Xue, Yiquan -- Han, Yanmei -- Lin, Li -- Wu, Cong -- Xu, Sheng -- Jiang, Zhengping -- Xu, Junfang -- Liu, Qiuyan -- Cao, Xuetao -- New York, N.Y. -- Science. 2014 Apr 18;344(6181):310-3. doi: 10.1126/science.1251456.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24744378" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Marrow Cells/cytology ; Cell Differentiation ; Chromatin/metabolism ; Cytoplasm/metabolism ; Dendritic Cells/*cytology/*immunology/physiology ; Epigenesis, Genetic ; Gene Expression Regulation ; Histones/metabolism ; Humans ; Lymphocyte Activation ; Mice ; Monocytes/cytology ; Nucleic Acid Conformation ; Phosphorylation ; Protein Tyrosine Phosphatase, Non-Receptor Type 6/metabolism ; RNA, Long Noncoding/*metabolism ; STAT3 Transcription Factor/*metabolism ; T-Lymphocytes/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1 (2013)
    Nature Publishing Group (NPG)
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    Publication Date: 2013-03-08
    Description: TH17 cells (interleukin-17 (IL-17)-producing helper T cells) are highly proinflammatory cells that are critical for clearing extracellular pathogens and for inducing multiple autoimmune diseases. IL-23 has a critical role in stabilizing and reinforcing the TH17 phenotype by increasing expression of IL-23 receptor (IL-23R) and endowing TH17 cells with pathogenic effector functions. However, the precise molecular mechanism by which IL-23 sustains the TH17 response and induces pathogenic effector functions has not been elucidated. Here we used transcriptional profiling of developing TH17 cells to construct a model of their signalling network and nominate major nodes that regulate TH17 development. We identified serum glucocorticoid kinase 1 (SGK1), a serine/threonine kinase, as an essential node downstream of IL-23 signalling. SGK1 is critical for regulating IL-23R expression and stabilizing the TH17 cell phenotype by deactivation of mouse Foxo1, a direct repressor of IL-23R expression. SGK1 has been shown to govern Na(+) transport and salt (NaCl) homeostasis in other cells. We show here that a modest increase in salt concentration induces SGK1 expression, promotes IL-23R expression and enhances TH17 cell differentiation in vitro and in vivo, accelerating the development of autoimmunity. Loss of SGK1 abrogated Na(+)-mediated TH17 differentiation in an IL-23-dependent manner. These data demonstrate that SGK1 has a critical role in the induction of pathogenic TH17 cells and provide a molecular insight into a mechanism by which an environmental factor such as a high salt diet triggers TH17 development and promotes tissue inflammation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637879/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637879/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Chuan -- Yosef, Nir -- Thalhamer, Theresa -- Zhu, Chen -- Xiao, Sheng -- Kishi, Yasuhiro -- Regev, Aviv -- Kuchroo, Vijay K -- 1P01HG005062-01/HG/NHGRI NIH HHS/ -- 1P50HG006193-01/HG/NHGRI NIH HHS/ -- AI045757/AI/NIAID NIH HHS/ -- AI073748/AI/NIAID NIH HHS/ -- DP1 CA174427/CA/NCI NIH HHS/ -- DP1 OD003958/OD/NIH HHS/ -- DP1-OD003958-01/OD/NIH HHS/ -- K01 DK090105/DK/NIDDK NIH HHS/ -- K01DK090105/DK/NIDDK NIH HHS/ -- NS030843/NS/NINDS NIH HHS/ -- NS045937/NS/NINDS NIH HHS/ -- P01 AI045757/AI/NIAID NIH HHS/ -- P01 AI073748/AI/NIAID NIH HHS/ -- P50 HG006193/HG/NHGRI NIH HHS/ -- R01 NS030843/NS/NINDS NIH HHS/ -- R01 NS045937/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Apr 25;496(7446):513-7. doi: 10.1038/nature11984. Epub 2013 Mar 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23467085" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation/*drug effects ; Encephalomyelitis, Autoimmune, Experimental/chemically ; induced/immunology/metabolism/pathology ; Forkhead Transcription Factors/metabolism ; HEK293 Cells ; Humans ; Immediate-Early Proteins/deficiency/genetics/*metabolism ; Interferon-gamma/biosynthesis/immunology ; Interleukin-17/biosynthesis/immunology/*metabolism ; Mice ; Phenotype ; Phosphorylation/drug effects ; Protein-Serine-Threonine Kinases/deficiency/genetics/*metabolism ; Receptors, Interleukin/biosynthesis/immunology ; Sodium Chloride/*pharmacology ; Sodium Chloride, Dietary/pharmacology ; Th17 Cells/*drug effects/enzymology/immunology/*pathology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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