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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Ikaros Zinc Finger Transcription Factors: Regulators of Cytokine Signaling Pathways and CD4+ T Helper Cell Differentiation
Michael D. Powell,Kaitlin A. Read,Kaitlin A. Read,Bharath K. Sreekumar,Kenneth J. Oestreich,Kenneth J. Oestreich +5 more
TL;DR: A review of the increasingly prominent role for IkZF transcription factors in the differentiation of effector CD4+ T helper cell subsets suggests that the distinct cell-specific cytokine environments responsible for the development of each subset result in differential expression of IkZf factors across T helper populations.
Journal ArticleDOI
Alginate/gelatin encapsulation promotes NK cells differentiation potential of bone marrow resident C-kit+ hematopoietic stem cells.
TL;DR: In this article, the effect of alginate-gelatin encapsulation on NK cell differentiation potential of C-kit+ cells was investigated, and it was concluded that the effects of encapsulation could be resulted from the secreted cytokines of interleukin (IL)-2, IL-3, IL 7, and IL 12 as well as the increased telomere length.
Journal ArticleDOI
The new entries in the therapeutic armamentarium: The small molecule JAK inhibitors.
TL;DR: Across the class, a characteristic safety signal is emerging with viral opportunistic infections, particularly herpes zoster, and emerging data with selective JAK1 inhibitors upadacitinib and filgotinib looks very promising.
Journal ArticleDOI
Emerging systemic JAK inhibitors in the treatment of atopic dermatitis: a review of abrocitinib, baricitinib, and upadacitinib
TL;DR: Clinical data available from various trials and reports on the safety and efficacy of abrocit inib, baricitinib, and upadacitinib are summarized, the three oral systemic JAK inhibitors used in the treatment of AD.
Journal ArticleDOI
Dimethyl fumarate induces ferroptosis and impairs NF-κB/STAT3 signaling in DLBCL
Anja Schmitt,Wendan Xu,Philip Bucher,Melanie Grimm,Martina Konantz,Heike Horn,Heike Horn,Myroslav Zapukhlyak,Philipp Berning,Marc Brändle,Mohamed Ali Jarboui,Caroline Schönfeld,Karsten Boldt,Andreas Rosenwald,German Ott,Michael Grau,Pavel Klener,Petra Vockova,Claudia Lengerke,Georg Lenz,Klaus Schulze-Osthoff,Klaus Schulze-Osthoff,Stephan Hailfinger,Stephan Hailfinger +23 more
TL;DR: In this article, the authors demonstrate a broad antitumor effect of dimethyl fumarate (DMF) on diffuse large B-cell lymphoma (DLBCL) subtypes, which is mediated by the induction of ferroptosis.
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.