SOCS1 and SOCS3 Target IRF7 Degradation To Suppress TLR7-Mediated Type I IFN Production of Human Plasmacytoid Dendritic Cells

Yu, Chunfeng; Peng, Wenming; Schlee, Martin; Barchet, Winfried; Eis‐Hübinger, Anna Maria; Kolanus, Waldemar; Geyer, Matthias; Schmitt, Sebastian; Steinhagen, Folkert; Oldenburg, Johannes; Novak, Natalija

doi:10.4049/jimmunol.1700510

Cited by 55 publications

(48 citation statements)

References 53 publications

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“…Most previous studies have demonstrated that SOCS1 mainly targets the JAK-STAT signaling pathways. Recent studies have presented direct evidence that SOCS1 downregulates type I IFN production (24). The results of this study indicate that SOCS1 not only suppressed IFN-b expression but also inhibited the expression of ISGs, which are stimulated by IFN ( Supplemental Fig.…”

Section: Discussionsupporting

confidence: 57%

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Porcine Reproductive and Respiratory Syndrome Virus Enhances Self-Replication via AP-1–Dependent Induction of SOCS1

Luo

Chen

Qiao

et al. 2020

The Journal of Immunology

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Porcine reproductive and respiratory syndrome virus (PRRSV) has caused tremendous economic losses in the swine industry since its emergence in the late 1980s. PRRSV exploits various strategies to evade immune responses and establish chronic persistent infections. Suppressor of cytokine signaling (SOCS) 1, a member of the SOCS family, is a crucial intracellular negative regulator of innate immunity. In this study, it was shown that SOCS1 can be co-opted by PRRSV to evade host immune responses, facilitating viral replication. It was observed that PRRSV induced SOCS1 production in porcine alveolar macrophages, monkey-derived Marc-145 cells, and porcine-derived CRL2843-CD163 cells. SOCS1 inhibited the expression of IFN-β and IFN-stimulated genes, thereby markedly enhancing PRRSV replication. It was observed that the PRRSV N protein has the ability to upregulate SOCS1 production and that nuclear localization signal–2 (NLS-2) is essential for SOCS1 induction. Moreover, SOCS1 upregulation was dependent on p38/AP-1 and JNK/AP-1 signaling pathways rather than classical type I IFN signaling pathways. In summary, to our knowledge, the findings of this study uncovered the molecular mechanism that underlay SOCS1 induction during PRRSV infection, providing new insights into viral immune evasion and persistent infection.

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Section: Discussionsupporting

confidence: 57%

“…Therefore, SOCS1 and SOCS3 are significant inhibitors of the JAK-STAT pathways. Recent studies have also shown that SOCS1 and SOCS3 strongly suppressed TLR7-mediated type I IFN production (24,25).…”

mentioning

confidence: 96%

Porcine Reproductive and Respiratory Syndrome Virus Enhances Self-Replication via AP-1–Dependent Induction of SOCS1

Luo

Chen

Qiao

et al. 2020

The Journal of Immunology

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“…These five genes were tightly involved with interferon signaling, for example, SOCS3 was termed as a key negative regulator of type I interferon signaling, which could target IRF7 degradation to suppress TLR7 mediated type I IFN production. 37,38 Same as SOCS3, NLRC5 also could negatively regulate the NFKB and type I IFN signaling pathway, even suppress the type I IFN secretion in plasmacytoid dendritic cells. 39,40 ISG20 and IFIT5 were termed as the classical interferon-induced genes, ISG20 exerts antiviral activity through upregulation of type I interferon response proteins, 41 IFIT5 also could positively regulate Figure 5.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of an interferon signature predicting prognosis and treatment response for glioblastoma

et al. 2019

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Background: Interferon treatment, as an important approach of anti-tumor immunotherapy, has been implemented in multiple clinical trials of glioma. However, only a small number of gliomas benefit from it. Therefore, it is necessary to investigate the clinical role of interferons and to establish robust biomarkers to facilitate its application. Materials and methods: This study reviewed 1,241 glioblastoma (GBM) and 1,068 lower grade glioma (LGG) patients from six glioma cohorts. The transcription matrix and clinical information were analyzed using R software, GraphPad Prism 7 and Medcalc, etc. Immunohistochemical (IHC) staining were performed for validation in protein level. Results: Interferon signaling was significantly enhanced in GBM. An interferon signature was developed based on five interferon genes with prognostic significance, which could reflect various interferon statuses. Survival analysis showed the signature could serve as an unfavorable prognostic factor independently. We also established a nomogram model integrating the risk signature into traditional prognostic factors, which increased the validity of survival prediction. Moreover, high-risk group conferred resistance to chemotherapy and high IFNB1 expression levels. Functional analysis showed that the high-risk group was associated with overloaded immune response. Microenvironment analysis and IHC staining found that high-risk group occupied a disorganized microenvironment which was characterized by an enrichment of M0 macrophages and neutrophils, but less infiltration of activated nature killing (NK) cells and M1 type macrophages. Conclusion: This interferon signature was an independent indicator for unfavorable prognosis and showed great potential for screening out patients who will benefit from chemotherapy and interferon treatment.

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“…Studies have shown that the activation of TLR7 in human plasmacytoid DCs can induce the expression of SOCS1 and SOCS3, while SOCS1 and SOCS3 will strongly inhibit TLR7-mediated IFN-I production (77). In addition, Yu Peng and his colleagues demonstrated that IRF7 combined with SOCS1 and SOCS3 and the SH2 domains of SOCS1 and SOCS3 promoted proteasome-mediated degradation of IRF7 through polyubiquitination related to lysine 48 (77). Moreover, studies have shown that TLR8 couples with SOCS-1 to control the TLR7-mediated antiviral immunity in the mouse central nervous system during West Nile virus (WNV) infection (78).…”

Section: Socs1 and Tlr Signalingmentioning

confidence: 99%

SOCS Proteins Participate in the Regulation of Innate Immune Response Caused by Viruses

et al. 2020

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The host immune system has multiple innate immune receptors that can identify, distinguish and react to viral infections. In innate immune response, the host recognizes pathogen-associated molecular patterns (PAMP) in nucleic acids or viral proteins through pathogen recognition receptors (PRRs), especially toll-like receptors (TLRs) and induces immune cells or infected cells to produce type I Interferons (IFN-I) and pro-inflammatory cytokines, thus when the virus invades the host, innate immunity is the earliest immune mechanism. Besides, cytokine-mediated cell communication is necessary for the proper regulation of immune responses. Therefore, the appropriate activation of innate immunity is necessary for the normal life activities of cells. The suppressor of the cytokine signaling proteins (SOCS) family is one of the main regulators of the innate immune response induced by microbial pathogens. They mainly participate in the negative feedback regulation of cytokine signal transduction through Janus kinase signal transducer and transcriptional activator (JAK/STAT) and other signal pathways. Taken together, this paper reviews the SOCS proteins structures and the function of each domain, as well as the latest knowledge of the role of SOCS proteins in innate immune caused by viral infections and the mechanisms by which SOCS proteins assist viruses to escape host innate immunity. Finally, we discuss potential values of these proteins in future targeted therapies.

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SOCS1 and SOCS3 Target IRF7 Degradation To Suppress TLR7-Mediated Type I IFN Production of Human Plasmacytoid Dendritic Cells

Cited by 55 publications

References 53 publications

Porcine Reproductive and Respiratory Syndrome Virus Enhances Self-Replication via AP-1–Dependent Induction of SOCS1

Porcine Reproductive and Respiratory Syndrome Virus Enhances Self-Replication via AP-1–Dependent Induction of SOCS1

Development and validation of an interferon signature predicting prognosis and treatment response for glioblastoma

SOCS Proteins Participate in the Regulation of Innate Immune Response Caused by Viruses

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