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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Journal ArticleDOI
Effects of ambient fine particulate matter on oxidative stress, inflammation, and janus kinase/signal transducer and activator of transcription signal molecules: a panel study of asthmatic adults in Taiyuan, China
Nannan Liu,Xiaoyan Ma,Jing Wang,Liangpo Liu,Bianzhuan Yang,Jianbiao Han,Jiayu Tian,Xin Wang,Caihong Wang,Danwen Wang,Hao Shi,G. Qiao,Haifang Liu,Zhihong Zhang +13 more
TL;DR: Ambient PM 2.5 aggravates asthma by systemic oxidative stress and inflammation, in which JAK/STAT signal molecules may be involved, and mediation of JAK2 in the associations between superoxide dismutase (SOD)/IL-12 and STAT4, JAK3 in the association between MDA and STAT6 is found.
Book ChapterDOI
Autoimmunity in Cellular Immunodeficiencies
TL;DR: In this paper, the dual function of the immune system is to defend the host against pathogens and not to be reactive against self-antigens, and the failure of these two missions is represented by primary immunodeficiencies (PID) and auto-immunity (AI), respectively.
Journal ArticleDOI
Impact of high temperature, CO2 and parasitic infection on inflammation, immunodepression and programmed cell death in Colossoma macropomum at the transcriptional level
TL;DR: In this article , the authors evaluated the synergistic effect of exposure to extreme climate change scenario (RCP8.5) during two exposure periods (7 and 30 days) and two levels of parasitism by monogeneans (low and high).
Journal ArticleDOI
One of the active ingredients in Paeoniae Radix Alba functions as JAK1 inhibitor in rheumatoid arthritis
Lu Xiao,Shudian Lin,Feng Zhan +2 more
TL;DR: In vitro and in vivo studies demonstrated that PB exerts its anti-inflammatory role via the inhibition of JAK1, and molecular docking analysis proved that PB was able to bind to the ATP binding site of Janus kinase (JAK)1, thereby acting as a potential inhibitor ofJAK1.
Journal ArticleDOI
PTP1B negatively regulates STAT1-independent Pseudomonas aeruginosa killing by macrophages.
TL;DR: It is demonstrated that protein tyrosine phosphatase-1B (PTP1B) is a critical negative regulator of P. aeruginosa infection response by macrophages and that STAT1 is dispensable for negative regulation of P .aerug inosa clearance bymacrophages.
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.