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
Citations
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Drug Retention Rates and the Safety of Janus Kinase Inhibitors in Elderly Patients with Rheumatoid Arthritis
Jumpei Temmoku,Masayuki Miyata,Eiji Suzuki,Yuya Sumichika,K. Saito,Shuhei Yoshida,Haruki Matsumoto,Yuya Fujita,Naoki Matsuoka,Tomoyuki Asano,Shuzo Sato,Kiyoshi Migita +11 more
TL;DR: In this article , the authors examined the real-world drug retention rate and safety data of Janus kinase inhibitors (JAKis) in elderly patients with rheumatoid arthritis (RA).
Journal ArticleDOI
The Complex Interplay Between JAK-STAT Pathway and ROS in Regulating Stem Cells During Inflammation and Cancer
TL;DR: In this paper , the orchestration and interaction between diverse molecular targets and the interleukin 6 (IL-6)-Janus Kinases (JAK)-STAT dependent signalling cascade within the inflammatory tumor niche is evidenced as the drivers of oncogenic signals for generation of cancers and CSCs.
Posted ContentDOI
Central nervous system immune response in postinfectious hydrocephalus
Albert M. Isaacs,Albert M. Isaacs,Sarah U. Morton,Sarah U. Morton,Mercedeh Movassagh,Qiang Zhang,Christine Hehnly,Lijun Zhang,Diego M. Morales,Shamim A. Sinnar,Jessica E. Ericson,Edith Mbabazi Kabachelor,Peter Ssenyonga,Justin Onen,Ronnie Mulondo,Mady Hornig,Benjamin C. Warf,James R. Broach,Raymond R. Townsend,David D. Limbrick,Joseph N. Paulson,Steven J. Schiff +21 more
TL;DR: This work integrated proteomics and RNA sequencing in cerebrospinal fluid, identifying gene pathways involving neutrophil, interleukin and interferon activity associated with this condition and required to develop strategies to reduce the risk of hydrocephalus during treatment of infection.
Journal ArticleDOI
JAK kinase inhibitors and varicella zoster virus infection in patients with rheumatoid arthritis. Systematic review of the literature
TL;DR: JAK kinase inhibitors (JAKi) are a new therapeutic option in the treatment of rheumatoid arthritis, but they are not without risks, especially the incidence of herpes zoster (HZ) as discussed by the authors .
Posted ContentDOI
Temporally integrated transcriptome analysis reveals ASFV pathology and host response dynamics
TL;DR: In this article , the authors used RNA-seq to analyze the viral and host transcriptome changes in porcine alveolar macrophages (PAMs) infected with a virulent strain (SY18) or an attenuated strain (HuB20) at different stages.
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.