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
Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality.
TL;DR: Tocilizumab is a blocker of IL-6R, which can effectively block IL- 6 signal transduction pathway, and is likely to become an effective drug for patients with severe COVID-19.
Journal ArticleDOI
Kinase inhibitors: the road ahead
TL;DR: An overview of the novel targets, biological processes and disease areas that kinase-targeting small molecules are being developed against, highlight the associated challenges and assess the strategies and technologies that are enabling efficient generation of highly optimized kinase inhibitors are provided.
Journal ArticleDOI
IFNγ: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy.
TL;DR: This Review focuses on recent advances in the understanding of the transcriptional, chromatin-based and metabolic mechanisms that underlie IFNγ-mediated polarization of macrophages to an ‘M1-like’ state, which is characterized by increased pro-inflammatory activity and macrophage resistance to tolerogenic and anti-inflammatory factors.
Journal ArticleDOI
Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer
TL;DR: The key roles of the IL-6 cytokine family in regulating innate and adaptive immunity, as well as other physiological responses are considered, which highlight the potential of targeting IL- 6 family members to treat inflammatory diseases and cancer.
Perturb-Seq: Dissecting Molecular Circuits with Scalable Single-Cell RNA Profiling of Pooled Genetic Screens
Atray Dixit,Atray Dixit,Oren Parnas,Biyu Li,Jenny Chen,Jenny Chen,Charles P. Fulco,Charles P. Fulco,Livnat Jerby-Arnon,Nemanja D. Marjanovic,Nemanja D. Marjanovic,Danielle Dionne,Tyler Burks,Raktima Raychowdhury,Britt Adamson,Thomas M. Norman,Eric S. Lander,Eric S. Lander,Eric S. Lander,Jonathan S. Weissman,Jonathan S. Weissman,Nir Friedman,Nir Friedman,Aviv Regev,Aviv Regev,Aviv Regev +25 more
TL;DR: Perturb-seq accurately identifies individual gene targets, gene signatures, and cell states affected by individual perturbations and their genetic interactions, and posit new functions for regulators of differentiation, the anti-viral response, and mitochondrial function during immune activation.
References
More filters
Journal ArticleDOI
SLIM is a nuclear ubiquitin E3 ligase that negatively regulates STAT signaling.
TL;DR: It is shown that SLIM is an ubiquitin E3 ligase that acts on STAT proteins to cause their proteosome-mediated degradation and enhance their dephosphorylation.
Journal ArticleDOI
A novel Ncr1-Cre mouse reveals the essential role of STAT5 for NK-cell survival and development
Eva Eckelhart,Wolfgang Warsch,Eva Zebedin,Olivia Simma,Dagmar Stoiber,Thomas Kolbe,Thomas Rülicke,Mathias Mueller,Emilio Casanova,Veronika Sexl,Veronika Sexl +10 more
TL;DR: The results of this study show that STAT5 has a cell-intrinsic role in NK-cell development and that Ncr1-iCreTg mice are a powerful novel tool with which to study NK- cell development, biology, and function.
Journal ArticleDOI
Immunoglobulin and T Cell Receptor Genes: IMGT® and the Birth and Rise of Immunoinformatics
TL;DR: IMGT, the international ImMunoGeneTics information system, is the global reference in immunogenetics and immunoinformatics and provides a high-quality and integrated system for the analysis of the genomic and expressed IG and TR repertoire of the adaptive immune responses.
Journal ArticleDOI
Genomic analyses reveal recurrent mutations in epigenetic modifiers and the JAK–STAT pathway in Sézary syndrome
Mark J. Kiel,Anagh A. Sahasrabuddhe,Delphine Rolland,Thirunavukkarasu Velusamy,Fuzon Chung,Matthew Schaller,Nathanael G. Bailey,Bryan L. Betz,Roberto N. Miranda,Pierluigi Porcu,John C. Byrd,L. Jeffrey Medeiros,Steven L. Kunkel,David W. Bahler,Megan S. Lim,Kojo S.J. Elenitoba-Johnson +15 more
TL;DR: This work integrates whole-genome sequencing, whole-exome sequencing and array comparative genomic hybridization-based copy-number analysis of SS samples to identify previously unknown recurrent loss-of-function aberrations targeting members of the chromatin remodelling/histone modification and trithorax families.
Journal ArticleDOI
Histone Deacetylases 6 and 9 and Sirtuin-1 Control Foxp3+ Regulatory T Cell Function Through Shared and Isoform-Specific Mechanisms
Ulf H. Beier,Liqing Wang,Rongxiang Han,Tatiana Akimova,Yujie Liu,Wayne W. Hancock,Wayne W. Hancock +6 more
TL;DR: Therapeutic inhibition of the histone deacetylases HDAC6, HDAC9, or sirtuin-1 (Sirt1) augments the suppressive functions of regulatory T cells (Tregs) that contain the transcription factor Foxp3 (Forkhead box P3) and is useful in organ transplant patients or patients with autoimmune diseases.