Journal ArticleDOI
Mechanisms and consequences of Jak–STAT signaling in the immune system
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TLDR
Recent advances in Jak–STAT biology are reviewed, focusing on immune cell function, disease etiology and therapeutic intervention, as well as broader principles of gene regulation and signal-dependent TFs.Abstract:
Kinases of the Jak ('Janus kinase') family and transcription factors (TFs) of the STAT ('signal transducer and activator of transcription') family constitute a rapid membrane-to-nucleus signaling module that affects every aspect of the mammalian immune system. Research on this paradigmatic pathway has experienced breakneck growth in the quarter century since its discovery and has yielded a stream of basic and clinical insights that have profoundly influenced modern understanding of human health and disease, exemplified by the bench-to-bedside success of Jak inhibitors ('jakinibs') and pathway-targeting drugs. Here we review recent advances in Jak-STAT biology, focusing on immune cell function, disease etiology and therapeutic intervention, as well as broader principles of gene regulation and signal-dependent TFs.read more
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ZEB1 promotes pathogenic Th1 and Th17 cell differentiation in multiple sclerosis
Yuan Qian,Gabriel Arellano,Igal Ifergan,Jean Lin,Caroline Snowden,Taehyeung Kim,Jane J. Thomas,Calvin Law,Tianxia Guan,Roumen Balabanov,Susan M. Kaech,Stephen D. Miller,Jaehyuk Choi +12 more
TL;DR: The role of Zinc finger E-box-binding homeobox (ZEB1) was identified in the development of multiple sclerosis (MS) in a mouse model as mentioned in this paper, where ZEB1 inhibited miR-101-3p that represses JAK2 expression and STAT3/STAT4 phosphorylation.
Journal ArticleDOI
Silymarin Restores Regulatory T Cells (Tregs) Function in Multiple Sclerosis (MS) Patients In Vitro.
Maryam Shariati,Vahid Shaygannejad,Faezeh Abbasirad,Fahimeh Hosseininasab,Mohammad Kazemi,Omid Mirmosayyeb,Nafiseh Esmaeil +6 more
TL;DR: The preliminary results suggest that the induction and activation of Tregs could be an underlying mechanism of the ancient used herbal medicine Silymarin, providing effective means against autoimmune and inflammatory diseases.
Journal ArticleDOI
NK Cells Require Cell-Extrinsic and -Intrinsic TYK2 for Full Functionality in Tumor Surveillance and Antibacterial Immunity.
Natalija Simonović,Agnieszka Witalisz-Siepracka,Katrin Meissl,Caroline Lassnig,Ursula Reichart,Thomas Kolbe,Thomas Kolbe,Matthias Farlik,Christoph Bock,Veronika Sexl,Mathias Müller,Birgit Strobl +11 more
TL;DR: It is shown that TYK2 is required for IFN-γ production by NK cells in response to IL-12 and for an efficient immune defense against Listeria monocytogenes and conditional ablation ofTYK2 in NK cells shows a less mature phenotype of Tyk2−/− NK cells, in line with the previously reported maturation-associated Ifng promoter demethylation.
Journal ArticleDOI
The RING finger protein family in health and disease
TL;DR: In this article , the potential contribution of dysregulated RNF proteins, except for TRIMs, to the pathogenesis of some diseases, including cancer, autoimmune diseases, and neurodegenerative disorder.
Journal ArticleDOI
Commensal Bacteria Regulate Gene Expression and Differentiation in Vertebrate Olfactory Systems Through Transcription Factor REST.
Elisa Casadei,Luca Tacchi,Colin R. Lickwar,Scott T. Espenschied,James M. Davison,Pilar Muñoz,John F. Rawls,Irene Salinas +7 more
TL;DR: It is shown that colonization of germ-free zebrafish and mice with microbiota leads to widespread transcriptional responses in olfactory organs as measured in bulk tissue transcriptomics and RT-qPCR and a new role for REST is revealed in sensory organs.
References
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Journal ArticleDOI
Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.
TL;DR: The authors showed that CD4+CD25+ cells contribute to maintaining self-tolerance by downregulating immune response to self and non-self Ags in an Ag-nonspecific manner, presumably at the T cell activation stage.
Journal ArticleDOI
Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins
TL;DR: A previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that phosphorylate substrate proteins called STATs (signal transducers and activators of transcription).
Journal ArticleDOI
A Gain-of-Function Mutation of JAK2 in Myeloproliferative Disorders
Robert Kralovics,Francesco Passamonti,Andreas Buser,Soon Siong Teo,Ralph Tiedt,Jakob Passweg,André Tichelli,Mario Cazzola,Radek C. Skoda +8 more
TL;DR: Genetic evidence and in vitro functional studies indicate that V617F gives hematopoietic precursors proliferative and survival advantages and a high proportion of patients with myeloproliferative disorders carry a dominant gain-of-function mutation of JAK2.
Journal ArticleDOI
Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders.
E. Joanna Baxter,Linda M. Scott,Peter J. Campbell,Clare L. East,Nasios Fourouclas,Soheila Swanton,George S. Vassiliou,Anthony J. Bench,Elaine M. Boyd,Natasha Curtin,Michael A. Scott,Wendy N. Erber,Anthony R. Green,Anthony R. Green +13 more
TL;DR: A single acquired mutation of JAK2 was noted in more than half of patients with a myeloproliferative disorder and its presence in all erythropoietin-independent erythroid colonies demonstrates a link with growth factor hypersensitivity, a key biological feature of these disorders.
Journal ArticleDOI
A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera
Chloé James,Valérie Ugo,Jean-Pierre Le Couedic,Judith Staerk,François Delhommeau,Catherine Lacout,Loïc Garçon,Hana Raslova,Roland Berger,Annelise Bennaceur-Griscelli,Jean-Luc Villeval,Stefan N. Constantinescu,Nicole Casadevall,William Vainchenker +13 more
TL;DR: A clonal and recurrent mutation in the JH2 pseudo-kinase domain of the Janus kinase 2 (JAK2) gene in most (> 80%) polycythaemia vera patients leads to constitutive tyrosine phosphorylation activity that promotes cytokine hypersensitivity and induces erythrocytosis in a mouse model.