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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.

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miR-122 regulates the JAK-STAT signalling pathway by down-regulating EPO in the mammary gland during Streptococcus agalactiae-induced mastitis

TL;DR: It is demonstrated that, through its action on EPO, miR-122 may play an important role in S. agalactiae-induced mastitis by regulating the JAK-STAT signalling pathway.
Journal ArticleDOI

Signal transducer and activator of transcription family is a prognostic marker associated with immune infiltration in endometrial cancer

TL;DR: Signal transducer and activator of transcription (STAT) is a unique protein family that binds to DNA and plays a vital role in regulating major physiological cellular processes.
Journal ArticleDOI

Multiomics Analysis Identifies SOCS1 as Restraining T Cell Activation and Preventing Graft‐Versus‐Host Disease

TL;DR: In this article , a multi-omics analysis of the transcriptome and chromatin structure of granulocyte-colony-stimulating-factor (G-CSF)-administered hyporesponsive T cells from healthy donors reveal that G-CSFs upregulates Suppressor of cytokine signaling 1 (SOCS1), which is a critical negative regulator for several inflammatory cytokines.
Journal ArticleDOI

Small Molecule Inhibitors of Interferon‐Induced JAK‐STAT Signalling

TL;DR: A first‐in‐class small molecule is found that blocks IFNγ activation of JAK‐STAT signalling and reduces bleeding in model of haemorrhagic colitis in vivo, and provides the basis for the development of pan‐IFN inhibitory drugs.
Journal ArticleDOI

Gene expression profiling of giant fibroadenomas of the breast.

TL;DR: In this paper, the authors identify up-and down-regulated genes in the giant fibroadenomas as compared to the normal fibroroadenoma, which is not malignant.
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.
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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).
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A Gain-of-Function Mutation of JAK2 in Myeloproliferative Disorders

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.
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Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders.

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

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.
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