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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DHAV-1 Inhibits Type I Interferon Signaling to Assist Viral Adaption by Increasing the Expression of SOCS3
Jinyan Xie,Mingshu Wang,Anchun Cheng,Xinxin Zhao,Mafeng Liu,Dekang Zhu,Shun Chen,Renyong Jia,Qiao Yang,Ying Wu,Shaqiu Zhang,Yunya Liu,Yanling Yu,Ling Zhang,Xiaoyue Chen +14 more
TL;DR: The DHAV-1 CH60 strain may inhibit the expression of IFNα by increasing the SOCS3 protein and SOCS 3 can in turn decrease STAT1 and STAT3 mRNA levels, thereby inhibiting the antiviral protein MX1 and ultimately promoting viral proliferation, indirectly assisting in viral adaptation in chicken embryos.
Journal ArticleDOI
Impact of Janus Kinase Inhibition on the Treatment of Axial Spondyloarthropathies.
TL;DR: Several trials were initiated to evaluate JAKinibs in PsA and axial spondyloarthritis, with one phase III trial of upadacitinib (selective JAK1 inhibitor) showing good therapeutic response in active radiographic axSpA.
Journal ArticleDOI
Transcriptomic Characterization of a Chicken Embryo Model Infected With Duck Hepatitis A Virus Type 1.
Jinyan Xie,Qiurui Zeng,Mingshu Wang,Xumin Ou,Yunchao Ma,Anchun Cheng,Xinxin Zhao,Mafeng Liu,Dekang Zhu,Shun Chen,Renyong Jia,Qiao Yang,Ying Wu,Shaqiu Zhang,Yunya Liu,Yanling Yu,Ling Zhang,Xiaoyue Chen +17 more
TL;DR: This study revealed that infection with DHAV-1 strain CH60 is associated with enhanced type I and II interferon responses, activated innate immune responses, elevated levels of suppressor of cytokine signaling 1 and 3 (SOCS1 and SOCS3) accompanied with abnormalities in multiple metabolic pathways.
Journal ArticleDOI
Cytokines that Modulate the Differentiation of Th17 Cells in Autoimmune Uveitis.
Kailei Guo,Xiaomin Zhang +1 more
TL;DR: In this paper, the authors discuss the structures, mechanisms, and targeted drugs of cytokines, including interleukin (IL)-6, transforming growth factor-β1 (TGF-β 1), IL-1β, IL-23, IL27, IL35, IL2, IL4, IL21, and interferon (IFN)-γ, which have an important influence on the differentiation of Th17 cells and discuss their potential as therapeutic targets for treating autoimmune uveitis.
Journal ArticleDOI
Adult hippocampal neurogenesis in the context of lipopolysaccharide-induced neuroinflammation: A molecular, cellular and behavioral review.
Eduardo Domínguez-Rivas,Evangelina Avila-Muñoz,Stephan W. Schwarzacher,Angélica Zepeda,Angélica Zepeda +4 more
TL;DR: A comprehensive overview of the current knowledge on the effects of systemic and central administration of LPS upon the different stages of neurogenesis and discuss their effects at the molecular, cellular, and behavioral levels can be found in this article.
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.