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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Baricitinib Attenuates Autoimmune Phenotype and Podocyte Injury in a Murine Model of Systemic Lupus Erythematosus
Jaeseon Lee,Youngjae Park,Se Gwang Jang,Seung-Min Hong,Young-Seok Song,Min-Jun Kim,Seung-Ye Baek,Sung-Hwan Park,Seung-Ki Kwok +8 more
TL;DR: Baricitinib, a selective inhibitor for janus kinase (JAK) 1 and JAK2, is approved for use in rheumatoid arthritis as discussed by the authors, which is a potential candidate targeted by JAK inhibitors because of the relationship between its pathogenesis and signal transducer and activator of transcription (STAT) mediated cytokines such as type I interferons.
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Pathogenic insights from genetic causes of autoinflammatory inflammasomopathies and interferonopathies
TL;DR: In this article , a review provides insights into the pathogenesis and genetic causes of these "prototypic" diseases caused by gain-of-function mutations in IL-1-activating inflammasomes (inflammasomopathies) and in interferonactivating pathways (interferonopathies), including STING-associated vasculopathy with onset in infancy, Aicardi-Goutieres syndrome, and proteasome-associated autoinflammatory syndromes that link activation of the viral sensors STING, "self" nucleic acid metabolism, and the ubiquitin-proteasome system to human diseases.
Journal ArticleDOI
Predictors of drug survival for biologic and targeted synthetic DMARDs in rheumatoid arthritis: Analysis from the TRA Clinical Electronic Registry.
Ching-Tsai Lin,Wen-Nan Huang,Wen-Chan Tsai,Jun-Peng Chen,Wei-Ting Hung,Tsu-Yi Hsieh,Hsin-Hua Chen,Chia-Wei Hsieh,Kuo-Lung Lai,Kuo-Tung Tang,Chih-Wei Tseng,Der-Yuan Chen,Yi-Hsin Chen,Yi-Ming Chen +13 more
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Journal ArticleDOI
Insights into the role of the JAK/STAT signaling pathway in graft-versus-host disease.
Ramzi Abboud,Jaebok Choi,Peter G. Ruminski,Mark A. Schroeder,Sena Kim,Camille N. Abboud,John F. DiPersio +6 more
TL;DR: Preclinical and clinical evidence for the role of JAK/STAT signaling in the development and maintenance of GVHD and the utility of blocking agents at preventing and treating GV HD are reviewed.
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.