Suppressors of Cytokine Signaling (SOCS) Proteins and JAK/STAT Pathways Regulation of T-Cell Inflammation by SOCS1 and SOCS3
01 May 2011-Arteriosclerosis, Thrombosis, and Vascular Biology (Lippincott Williams & Wilkins)-Vol. 31, Iss: 5, pp 980-985
TL;DR: Various cytokines are involved in the regulation of the immune system and inflammation, and SOCS proteins bind to janus kinase and to certain cytokine receptors and signaling molecules, thereby suppressing further signaling events.
Abstract: Various cytokines are involved in the regulation of the immune system and inflammation. Dysregulation of cytokine signaling can cause a variety of diseases, including allergy, autoimmune diseases, inflammation, and cancer. Most cytokines use the so-called janus kinase/signal transducer and activator of transcription pathway, and this pathway is negatively regulated by suppressors of cytokine signaling (SOCS) proteins. SOCS proteins bind to janus kinase and to certain cytokine receptors and signaling molecules, thereby suppressing further signaling events. Studies have shown that SOCS proteins are key physiological regulators of inflammation. Recent studies have also demonstrated that SOCS1 and SOCS3 are important regulators of adaptive immunity.
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TL;DR: The regulation and function of IL-33 and ST2 are highlighted and their roles in homeostasis, damage, and inflammation are reviewed, suggesting a conceptual framework for future studies.
463 citations
TL;DR: This review represents how the JAK-STAT pathway is generally regulated and then in Th cell subsets in more detail and introduces novel targeted strategies as promising therapeutic approaches in the treatment of immune disorders.
Abstract: The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays critical roles in orchestrating of immune system, especially cytokine receptors and they can modulate the polarization of T helper cells. This pathway is regulated by an array of regulator proteins, including Suppressors of Cytokine Signaling (SOCS), Protein Inhibitors of Activated STATs (PIAS) and Protein Tyrosine Phosphatases (PTPs) determining the initiation, duration and termination of the signaling cascades. Dysregulation of the JAK-STAT pathway in T helper cells may result in various immune disorders. In this review, we represent how the JAK-STAT pathway is generally regulated and then in Th cell subsets in more detail. Finally, we introduce novel targeted strategies as promising therapeutic approaches in the treatment of immune disorders. Studies are ongoing for identifying the other regulators of the JAK-STAT pathway and designing innovative therapeutic strategies. Therefore, further investigation is needed.
457 citations
Cites background from "Suppressors of Cytokine Signaling (..."
...Deletion of SOCS1 enhances Treg proliferation, however, their function is defective [62]....
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...The absence of SOCS3 promotes Th17 development, causing highly pro-inflammatory responses [62]....
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TL;DR: In this article, the authors discuss the current knowledge about the composition, activation, and regulation of the JAK/STAT pathway and highlight the role of the pathway and its inhibitors in various diseases.
Abstract: The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway was discovered more than a quarter-century ago. As a fulcrum of many vital cellular processes, the JAK/STAT pathway constitutes a rapid membrane-to-nucleus signaling module and induces the expression of various critical mediators of cancer and inflammation. Growing evidence suggests that dysregulation of the JAK/STAT pathway is associated with various cancers and autoimmune diseases. In this review, we discuss the current knowledge about the composition, activation, and regulation of the JAK/STAT pathway. Moreover, we highlight the role of the JAK/STAT pathway and its inhibitors in various diseases.
273 citations
TL;DR: The roles of SOCS1 and SOCS3 in T cell mediated inflammatory diseases are reviewed, which show that SOCS proteins are key physiological as well as pathological regulators of immune homeostasis.
Abstract: Cytokines play essential roles in innate and adaptive immunity. However, excess cytokines or dysregulation of cytokine signaling will cause a variety of diseases, including allergies, autoimmune diseases, inflammation, and cancer. Most cytokines utilize the so-called Janus kinase–signal transducers and activators of transcription pathway. This pathway is negatively regulated by various mechanisms including suppressors of cytokine signaling (SOCS) proteins. SOCS proteins bind to JAK or cytokine receptors, thereby suppressing further signaling events. Especially, suppressor of cytokine signaling-1 (SOCS1) and SOCS3 are strong inhibitors of JAKs, because these two contain kinase inhibitory region at the N-terminus. Studies using conditional knockout mice have shown that SOCS proteins are key physiological as well as pathological regulators of immune homeostasis. Recent studies have also demonstrated that SOCS1 and SOCS3 are important regulators of helper T cell differentiation and functions. This review focuses on the roles of SOCS1 and SOCS3 in T cell mediated inflammatory diseases.
217 citations
Cites background from "Suppressors of Cytokine Signaling (..."
...The SOCS proteins and CIS (also known as CISH) protein comprise a family of intracellular proteins (Yasukawa et al., 2003; Yoshimura et al., 2007; Tamiya et al., 2011)....
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...…play additional unexpected and important roles in many immunological processes (Chinen et al., 2011; Hiwatashi et al., 2011; Takahashi et al., 2011; Tamiya et al., 2011), atherosclerosis (Taleb et al., 2009), metabolism (Mori et al., 2004; Torisu et al., 2007), and cancer (Yoshida et al., 2004;…...
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...The absence of SOCS3 in helper T cells therefore generally inhibits Th1 and Th2 by producing IL-10 and TGF-β, but had dramatic pro-inflammatory effects under Th17 conditions (Tamiya et al., 2011)....
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TL;DR: Upregulation of miR-19a in asthma may be an indicator and a cause of increased TH2 cytokine production in the airways and direct targeting of the inositol phosphatase PTEN, the signaling inhibitor SOCS1 and the deubiquitinase A20 is identified.
Abstract: miRNAs 'tune' gene expression to orchestrate cell activity. Ansel and colleagues show that miR-19 modulates TH2 cytokine production by targeting TH2-specific as well as general T cell–activation pathways.
204 citations
References
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TL;DR: This review brings together data from recent studies on SOCS proteins and their role in immunity, and proposes a cohesive model of how cytokine signalling regulates immune-cell function.
Abstract: Suppressor of cytokine signalling (SOCS) proteins are inhibitors of cytokine signalling pathways. Studies have shown that SOCS proteins are key physiological regulators of both innate and adaptive immunity. These molecules positively and negatively regulate macrophage and dendritic-cell activation and are essential for T-cell development and differentiation. Evidence is also emerging of the involvement of SOCS proteins in diseases of the immune system. In this Review we bring together data from recent studies on SOCS proteins and their role in immunity, and propose a cohesive model of how cytokine signalling regulates immune-cell function.
1,424 citations
TL;DR: A pathway whereby cytokines regulate THi differentiation through a selective STAT transcription factor that functions to regulate lineage-specific gene expression is demonstrated.
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TL;DR: This review focuses on recent advances in the field and highlights some of the most active areas of Jak-Stat pathway research.
1,123 citations