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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Role of TRAFs in Signaling Pathways Controlling T Follicular Helper Cell Differentiation and T Cell-Dependent Antibody Responses.
TL;DR: The molecular interactions and the major signaling pathways controlling the differentiation of TFH cells are introduced and the contributions of TRAF proteins to these signaling pathways are highlighted.
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Effect of cornel iridoid glycoside on microglia activation through suppression of the JAK/STAT signalling pathway
Zhao Qu,Na Zheng,Yuzhen Wei,Yujing Chen,Yifan Zhang,Ming Zhang,Haoxiao Chang,Jianghong Liu,Houxi Ai,Xingchao Geng,Qi Wang,Linlin Yin +11 more
TL;DR: It is demonstrated that CIG delayed the onset of the EAE, ameliorated the severity of the symptoms and inhibited the activation of microglia in different brain regions and CIG might be a promising candidate for the prevention of neurological disorders such as multiple sclerosis.
Journal ArticleDOI
Seselin ameliorates inflammation via targeting Jak2 to suppress the proinflammatory phenotype of macrophages.
Lili Feng,Yi Sun,Pingping Song,Lisha Xu,Xingxin Wu,Xue-Feng Wu,Yan Shen,Yang Sun,Ling-Dong Kong,Xudong Wu,Qiang Xu +10 more
TL;DR: Evaluated the anti‐inflammatory activity of seselin in models of sepsis and investigated the underlying molecular mechanism(s) to find anti inflammatory agents found to be beneficial for the treatment ofsepsis.
Journal ArticleDOI
Hi- JAKi-ng Synovial Fibroblasts in Inflammatory Arthritis With JAK Inhibitors
TL;DR: This review uniquely challenges future study designs to better mimick the jakinib actions in broader cell communities, as occurring in vivo in the inflamed synovium.
Journal ArticleDOI
Degradation of WTAP blocks antiviral responses by reducing the m6A levels of IRF3 and IFNAR1 mRNA
Yong Ge,Tao Ling,Yao Wang,Yao Wang,Xin Jia,Xin Jia,Xiongmei Xie,Rong Chen,Shangwu Chen,Shaochun Yuan,Anlong Xu,Anlong Xu +11 more
TL;DR: In this article, the role of m6 A modification in type I interferon (IFN-I) signaling was investigated and it was shown that m6-methyladenosine (m6 A) is a chemical modification present in multiple RNA species and is most abundant in mRNAs.
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.