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IL-6 prevents Th2 cell polarization by promoting SOCS3-dependent suppression of IL-2 signaling

Cellular & Molecular Immunology 2023年第6期20卷 651-665页

作者： Holly Bachus Erin McLaughlin Crystal Lewis Amber M.Papillion Etty N.Benveniste dave durell hill Alexander F.Rosenberg AndréBallesteros-Tato Beatriz León Department of Medicine Division of Clinical Immunology and RheumatologyUniversity of Alabama at BirminghamBirminghamALUSA Department of Microbiology University of Alabama at BirminghamBirminghamALUSA Department of Cell Developmental and Integrative BiologyUniversity of Alabama at BirminghamBirminghamALUSA informatics Institute University of Alabama at BirminghamBirminghamALUSA Alexion Pharmaceuticals Inc.New HavenCTUSA

Defective interleukin-6 (IL-6) signaling has been associated with Th2 bias and elevated IgE levels. However, the underlying mechanism by which IL-6 prevents the development of Th2-driven diseases remains unknown. Using a model of house dust mite (HDM)-induced Th2 cell differentiation and allergic airway inflammation, we showed that IL-6 signaling in allergen-specific T cells was required to prevent Th2 cell differentiation and the subsequent IgE response and allergic inflammation. Th2 cell lineage commitment required strong sustained IL-2 signaling. We found that IL-6 turned off IL-2 signaling during early T-cell activation and thus inhibited Th2 priming. Mechanistically, IL-6-driven inhibition of IL-2 signaling in responding T cells was mediated by upregulation of Suppressor Of Cytokine Signaling 3 (SOCS3). This mechanism could be mimicked by pharmacological Janus Kinase-1 (JAK1) inhibition. Collectively, our results identify an unrecognized mechanism that prevents the development of unwanted Th2 cell responses and associated diseases and outline potential preventive interventions.

关键词： Th2 cell polarization IL-6 IL-2 SOCS3 JAK1 inhibitor

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N-acetylcysteine treats intravenous amiodarone induced liver injury

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World Journal of Gastroenterology 2015年第9期21卷 2816-2819页

作者： Matthew L Mudalel Kartikeya P dave James P Hummel Steven F Solga Department of Medicine Division of GastroenteorlogySt. Luke’s University Hospital and Temple School of MedicineBethlehemPA 18015United States Department of Medicine Montefiore Medical CenterBronxNY 10461United States Department of Medicine Division of Cardiology University of North Carolina Chapel Hill NC 27514United States

We report a case of intravenous(IV) amiodarone drug induced liver injury(DILI).The patient received IV N-acetylcysteine(NAC) which resulted in a rapid improvement in liver *** the specific mechanisms for the pathogenesis of IV amiodaroneDILI and the therapeutic action of IV NAC are both unknown, this case strongly implies at least some *** IV amiodarone is indicated for the treatment of serious cardiac arrhythmias in an intensive care unit setting, some degree of ischemic hepatitis is likely a cofactor in most cases.

关键词： N-acetylcysteine Amiodarone Drug induced liver inj

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Guacamole Joe

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英语沙龙（高中） 2015年第7期 60-61页

作者： Lori Polydoros dave Clegg

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Nature：大规模研究揭示生命所必需的基因

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现代生物医学进展 2016年第31期16卷 I0002-I0003页

作者： Dickinson, Mary E. Flenniken, Ann M. Ji, Xiao Teboul, Lydia Wong, Michael D. White, Jacqueline K. Meehan, Terrence F. Weninger, Wolfgang J. Westerberg, Henrik Adissu, Hibret Baker, Candice N. Bower, Lynette Brown, James M. Caddle, L. Brianna Chiani, Francesco Clary, dave Cleak, James Daly, Mark J. Denegre, James M. Doe, Brendan Dolan, Mary E. Edie, Sarah M. Fuchs, Helmut Gailus-Durner, Valerie Galli, Antonella Gambadoro, Alessia Gallegos, Juan Guo, Shiying Horner, Neil R. Hsu, Chih-Wei Johnson, Sara J. Kalaga, Sowmya Keith, Lance C. Lanoue, Louise Lawson, Thomas N. Lek, Monkol Mark, Manuel Arschall, Susan M. Mason, Jeremy McElwee, Melissa L. Newbigging, Susan Nutter, Lauryl M. J. Peterson, Kevin A. Ramirez-Solis, Ramiro Rowland, Douglas J. Ryder, Edward Samocha, Kaitlin E. Seavitt, John R. Selloum, Mohammed Szoke-Kovacs, Zsombor Tamura, Masaru Trainor, Amanda G. Tudose, Ilinca Wakana, Shigeharu Warren, Jonathan Wendling, Olivia West, David B. Wong, Leeyean Yoshiki, Atsushi MacArthur, Daniel G. Tocchini-Valentini, Glauco P. Gao, Xiang Flicek, Paul Bradley, Allan Skarnes, William C. Justice, Monica J. Parkinson, Helen E. Moore, Mark Wells, Sara Braun, Robert E. Svenson, Karen L. de Angelis, Martin Hrabe Herault, Yann Mohun, Tim Mallon, Ann-Marie Henkelman, R. Mark Brown, Steve D. M. Adams, David J. Lloyd, K. C. Kent McKerlie, Colin Beaudet, Arthur L. Bucan, Maja Murray, Stephen A. Dept Mol Physiol & Biophys Houston TX 77030 USA Toronto Ctr Phenogen Toronto ON M5T 3H7 Canada Mt Sinai Hosp Toronto ON M5G 1X5 Canada Univ Penn Perelman Sch Med Genom & Computat Biol Program Philadelphia PA 19104 USA Med Res Council Harwell Mammalian Genet Unit Harwell OX11 0RD Oxon England Mary Lyon Ctr Harwell OX11 0RD Oxon England Hosp Sick Children Mouse Imaging Ctr Toronto ON M5T 3H7 Canada Wellcome Trust Sanger Inst Wellcome Trust Genome Campus Cambridge CB10 1SA England European Bioinformat Inst European Mol Biol Lab Wellcome Trust Genome Campus Cambridge CB10 1SD England Med Univ Vienna Ctr Anat & Cell Biol A-1090 Vienna Austria Hosp Sick Children 555 Univ Ave Toronto ON M5G 1X8 Canada Jackson Lab 600 Main St Bar Harbor ME 04609 USA Univ Calif Davis Mouse Biol Program Davis CA 95618 USA Italian Natl Res Council CNR Inst Cell Biol & Neurobiol Monterotondo Mouse Clin I-00015 Monterotondo Italy Massachusetts Gen Hosp Analyt & Translat Genet Unit Boston MA 02114 USA Broad Inst MIT & Harvard Program Med & Populat Genet Cambridge MA 02142 USA German Res Ctr Environm Hlth Helmholtz Zentrum Munchen Inst Expt Genet D-85764 Neuherberg Germany German Mouse Clin D-85764 Neuherberg Germany Baylor Coll Med Dept Mol & Human Genet Houston TX 77030 USA Nanjing Univ Nanjing Biomed Res Inst Collaborat Innovat Ctr Genet & Dev SKL Pharmaceut Biotechnol & Model Anim Res Ctr Nanjing 210061 Jiangsu Peoples R China Univ Strasbourg ICS Infrastruct Natl PHENOMIN F-67404 Illkirch Graffenstaden France Univ Strasbourg INSERM CNRS IGBMC F-67404 Illkirch Graffenstaden France RIKEN BioResource Ctr Tsukuba Ibaraki 3050074 Japan Childrens Hosp Oakland Res Inst Oakland CA 94609 USA IMPC San Anselmo CA 94960 USA Tech Univ Munich Sch Life Sci Weihenstephan Chair Expt Genet D-81675 Freising Weihenstephan Germany German Ctr Diabet Res DZD D-85764 Neuherberg Germany Francis Crick Inst Mill Hill Lab Mill Hill London NW1 1AT England Univ Penn Perlman

在哺乳动物基因组中。大约三分之一的基因是生命所必需的。在一项新的研究中，来自美国贝勒医学院等多个机构的研究人员描述了这些基因的大规模发现。以及它将如何影响对哺乳动物发育和人类疾病的理解。相关研究结果在线发表在Nature期... 详细信息

在哺乳动物基因组中。大约三分之一的基因是生命所必需的。在一项新的研究中，来自美国贝勒医学院等多个机构的研究人员描述了这些基因的大规模发现。以及它将如何影响对哺乳动物发育和人类疾病的理解。相关研究结果在线发表在Nature期刊上，论文标题为“High—throughput discovery of novel developmental phenotypes”。

关键词：动物基因组生命哺乳动物研究人员人类疾病医学院

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