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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Journal ArticleDOI
Immune activation during Paenibacillus brain infection in African infants with frequent cytomegalovirus co-infection
Albert M. Isaacs,Albert M. Isaacs,Sarah U. Morton,Sarah U. Morton,Mercedeh Movassagh,Qiang Zhang,Christine Hehnly,Lijun Zhang,Diego M. Morales,Shamim A. Sinnar,Jessica E. Ericson,Edith Mbabazi-Kabachelor,Peter Ssenyonga,Justin Onen,Ronnie Mulondo,Mady Hornig,Benjamin C. Warf,James R. Broach,Raymond R. Townsend,David D. Limbrick,Joseph N. Paulson,Steven J. Schiff +21 more
TL;DR: In this paper, a proteogenomic strategy was employed to confirm host immune response to Paenibacillus species and define the interplay within the host immune system network, which emphasized neuroinflammation, oxidative stress reaction, and extracellular matrix organization.
Journal ArticleDOI
CoGT: Ensemble Machine Learning Method and Its Application on JAK Inhibitor Discovery
TL;DR: In this article , the authors developed a novel ensemble model CoGT for DTI prediction using multilayer perceptron (MLP), which integrated graph-based models to extract non-Euclidean molecular structures and large pretrained models, specifically chemBERTa, to process simplified molecular input line entry systems.
Journal ArticleDOI
Understanding Aberrant Signaling to Elude Therapy Escape Mechanisms in Myeloproliferative Neoplasms
Maria Teresa Bochicchio,Valeria Di Battista,Pietro Poggio,Giovanna Carrà,Alessandro Morotti,Mara Brancaccio,Alessandro Lucchesi +6 more
TL;DR: Molecular mechanisms at the basis of disease persistence and new therapeutic attempts to overcome them are discussed in the review and unexpected connections among signal transduction pathways highlighted in neoplastic cells suggest new strategies to overcome neoplastics cell adaptation.
Dissertation
New findings in the genetic landscape of systemic sclerosis
TL;DR: In this paper, a tesis doctoral se centro en el estudio del componente genetico subyacente a the SSc: PPARG, IL12RB1, and TYK2.
Posted ContentDOI
STAT3 expression in dendritic cells protects mice from colitis by a gut microbiome-dependent mechanism
Jing Liu,K. Szilagyi,Maegan L. Capitano,Abhirami K. Iyer,Johnny J. He,Matthew R. Olson,Jianqiu Du,W. Van Der Pol,Casey D. Morrow,Baohua Zhou,Mark H. Kaplan,Alexander L. Dent,Randy R. Brutkiewicz +12 more
TL;DR: In this paper, the authors used a mouse model in which STAT3 expression is deleted in CD11c+ (i.e., dendritic) cells (STAT3 cKO); these mice developed an ulcerative colitis-like disease, colon carcinoma and myelodysplastic syndrome-like diseases.
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.