Journal ArticleDOI
Mechanisms and consequences of Jak–STAT signaling in the immune system
Reads0
Chats0
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
More filters
Journal ArticleDOI
JAK and STAT members in channel catfish: Identification, phylogenetic analysis and expression profiling after Edwardsiella ictaluri infection.
Yulin Jin,Tao Zhou,Ning Li,Shikai Liu,Xiaoyan Xu,Ying Pan,Suxu Tan,Huitong Shi,Yujia Yang,Zihao Yuan,W. H. Wang,Jian Luo,Dongya Gao,Rex A. Dunham,Zhanjiang Liu +14 more
TL;DR: The increased expression of JAK and STAT members in tested tissues suggested their crucial function in defending the host against pathogen invasion, and supported the notion that high STAT1 expression are involved in defense against pathogens.
Journal ArticleDOI
JAK-STAT Targeting Offers Novel Therapeutic Opportunities in Sepsis
Raphaël Clere-Jehl,Alexandre Mariotte,Ferhat Meziani,Seiamak Bahram,Philippe Georgel,Julie Helms +5 more
TL;DR: Why the Janus kinase-signal transducer and activator of transcription (JAK-STAT)-dependent signaling pathway is involved in both manifestations of sepsis and why its central position makes it a potential biomarker and therapeutic target is illustrated.
Journal ArticleDOI
Low-dose decitabine modulates T-cell homeostasis and restores immune tolerance in immune thrombocytopenia
Panpan Han,Yu Hou,Yajing Zhao,Yang Liu,Tianshu Yu,Yunqi Sun,Haoyi Wang,Pengcheng Xu,Guosheng Li,Tao Sun,Xiang Hu,Xinguang Liu,Lizhen Li,Jun Peng,Hai Zhou,Ming Hou +15 more
TL;DR: In this paper, the effect of decitabine on T-cell subpopulations in ITP in vitro and in vivo was analyzed and it was shown that low-dose decitrabine promoted the generation and differentiation of regulatory T (Treg) cells and augmented their immunosuppressive function.
Journal ArticleDOI
Thromboembolic Adverse Drug Reactions in Janus Kinase (JAK) Inhibitors: Does the Inhibitor Specificity Play a Role?
TL;DR: In this article, the authors discuss data on the risk of thromboembolic side effects, with special emphasis on the mechanism that may be responsible for this increased risk, such that preferentially blocking one signaling pathway upsets the balance between pro and anti-thrombotic activities.
Journal ArticleDOI
JAK1-mediated Sirt1 phosphorylation functions as a negative feedback of the JAK1-STAT3 pathway
Wenhui Wang,Fei Li,Yuanming Xu,Juncheng Wei,Yana Zhang,Heeyoung Yang,Beixue Gao,Guohua Yu,Deyu Fang +8 more
TL;DR: JAK1 is identified as a previously unappreciated tyrosine kinase of Sirt1 and a novel negative feedback of the JAK1-STAT3 pathway is revealed and attenuates IL-6 activity in protecting cancer cells from chemotherapeutic drug–induced apoptosis.
References
More filters
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.