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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Contemporary narrative review of treatment options for COVID-19.
TL;DR: In this article, the authors present the key clinical evidence and progress in promising COVID-19 therapeutics, as well as summarize the experience and lessons learned from the development of the current therapeutics.
Journal ArticleDOI
Tofacitinib alters STAT3 signaling and leads to endometriosis lesion regression.
TL;DR: In this paper, the effect of Tofacitinib, a JAK inhibitor in widespread clinical use, on JAK/STAT signaling in endometriosis and lesion growth was investigated.
Journal ArticleDOI
Interleukin-35 promotes early endothelialization after stent implantation by regulating macrophage activation
Xianglan Liu,Ruoxi Zhang,Jingbo Hou,Jian Wu,Maomao Zhang,Shaohong Fang,Xuedong Wang,Xingtao Huang,Jinwei Tian,Li Hulun,Yong Sun,Bo Yu +11 more
TL;DR: A crucial role is identified for IL-35 in inducing the activation of an anti-inflammatory M2-like macrophage phenotype and this work highlights a new therapeutic strategy for early stent endothelialization.
Journal ArticleDOI
Identification of novel long non-coding RNAs involved in bisphenol A induced immunotoxicity in fish primary macrophages.
TL;DR: The potential role of lncRNAs in immunotoxicity of bisphenol compounds in red common carp HK macrophages is demonstrated, and the results provide evidence for further exploring lncRNA's role in EDC-induced toxicity in aquatic organisms.
Journal ArticleDOI
Chrysophanol attenuated isoproterenol-induced cardiac hypertrophy by inhibiting Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway
TL;DR: It is found that chrysophanol could protect against isoproterenol (ISO)‐induced cardiac hypertrophy both in vitro and in vivo, and may be a potential candidate compound for the prevention and treatment ofhypertrophy‐related cardiomyopathy.
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.