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
Hydroxysafflor Yellow A Confers Neuroprotection from Focal Cerebral Ischemia by Modulating the Crosstalk Between JAK2/STAT3 and SOCS3 Signaling Pathways.
Lu Yu,Zhili Liu,Wendi He,Huifen Chen,Zelin Lai,Yanhong Duan,Xiaohua Cao,Jie Tao,Chuan Xu,Qiujuan Zhang,Zheng Zhao,Jun Zhang +11 more
TL;DR: This study demonstrates that HSYA might modulate the crosstalk between JAK2/STAT3 and SOCS3 signaling pathways that eventually contributed to its therapeutic roles against cerebral ischemic stroke.
Journal ArticleDOI
IL-12 and IL-23-Close Relatives with Structural Homologies but Distinct Immunological Functions.
TL;DR: Structural knowledge about receptor complex formation is essential for the development of new therapeutic strategies preventing and/or inhibiting cytokine:receptor interaction and intracellular signaling pathways.
Journal ArticleDOI
Posttranscriptional regulation of T helper cell fate decisions
Kai P. Hoefig,Vigo Heissmeyer +1 more
TL;DR: Hoefig and Heissmeyer review how microRNAs, long noncoding RNAs, RNA-binding proteins, and ubiquitin-modifying enzymes regulate T helper cell differentiation downstream of transcription.
Journal ArticleDOI
NCR+ ILC3 maintain larger STAT4 reservoir via T-BET to regulate type 1 features upon IL-23 stimulation in mice.
Yohei Mikami,Gianluca Scarno,Beatrice Zitti,Han-Yu Shih,Yuka Kanno,Angela Santoni,John J. O'Shea,Giuseppe Sciumè +7 more
TL;DR: It is found that the prototypical inducer of type 3 response, IL‐23, played a predominant role over IL‐12 by accessing STAT4 and preferentially inducing its phosphorylation in ILC3 expressing T‐BET, leading to predisposed potential for the type 1 response.
Journal ArticleDOI
Drosophila as a Model for Infectious Diseases.
J. Michael Harnish,J. Michael Harnish,Nichole Link,Nichole Link,Nichole Link,Shinya Yamamoto +5 more
TL;DR: The fruit fly melanogaster has been used to understand fundamental principles of genetics and biology for over a century as mentioned in this paper, and is now considered an essential tool to study mechanisms underlying numerous human genetic diseases.
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.