STAT3 regulates antiviral immunity by suppressing excessive interferon signaling

Li, Shasha; Liu, Siya; Yu, Ziding; Zhou, Wenzhuo; Zheng, Min; Gu, Rong; Hong, Jinxuan; Zhou, Yang; Chi, Xiaojuan; Guo, Guijie; Li, Xinxin; Chen, Na; Huang, Shile; Wang, Song; Chen, Ji‐Long

doi:10.1016/j.celrep.2023.112806

Cited by 8 publications

(3 citation statements)

References 57 publications

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“…32,[38][39][40] Hence, R406 may reduce viral replication and spread by inhibiting the inhibition of cellular autophagy mediated by the SYK/Akt/mTOR/p70S6K pathway in the late stage of infection. Furthermore, inhibition of STAT3 activation decreased the levels of IFN-γ and several important inflammation-related factors (e.g., IL-6 and IL-1β) levels, 41 which is consistent with our results of sera IFN-γ and IL-6 in the lungs of mice. IFN-γ or IL-6 have been demonstrated to be critically detrimental in acute severe pneumovirus infection.…”

Section: Discussionsupporting

confidence: 92%

Spleen tyrosine kinase inhibitor R406 has both antiviral and anti‐inflammatory effects on severe influenza A infection

Luo,

Gao,

Guo

et al. 2024

Journal of Medical Virology

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Death due to severe influenza is usually a fatal complication of a dysregulated immune response more than the acute virulence of an infectious agent. Although spleen tyrosine kinase (SYK) as a critical immune signaling molecule and therapeutic target plays roles in airway inflammation and acute lung injury, the role of SYK in influenza virus infection is not clear. Here, we investigated the antiviral and anti‐inflammatory effects of SYK inhibitor R406 on influenza infection through a coculture model of human alveolar epithelial (A549) and macrophage (THP‐1) cell lines and mouse model. The results showed that R406 treatment increased the viability of A549 and decreased the pathogenicity and mortality of lethal influenza virus in mice with influenza A infection, decreased levels of intracellular signaling molecules under the condition of inflammation during influenza virus infection. Combination therapy with oseltamivir further ameliorated histopathological damage in the lungs of mice and further delayed the initial time to death compared with R406 treatment alone. This study demonstrated that phosphorylation of SYK is involved in the pathogenesis of influenza, and R406 has antiviral and anti‐inflammatory effects on the treatment of the disease, which may be realized through multiple pathways, including the already reported SYK/STAT/IFNs‐mediated antiviral pathway, as well as TNF‐α/SYK‐ and SYK/Akt‐based immunomodulation pathway.

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Section: Discussionsupporting

confidence: 92%

Spleen tyrosine kinase inhibitor R406 has both antiviral and anti‐inflammatory effects on severe influenza A infection

Luo,

Gao,

Guo

et al. 2024

Journal of Medical Virology

View full text Add to dashboard Cite

show abstract

“…144 STAT3 signaling may also hinder the production of Type I IFNs, as recent evidence suggests that Type I IFN production increases when STAT3 is unphosphorylated. 145 As such STAT3 has a dual inhibitory role, where it acts to both suppress Type I IFN-mediated signaling and lowers its production. Given that exNK cell expansion and metabolic reprogramming is driven through STAT3, we sought to investigate the role of IFN signaling in these cells.…”

Section: Unveiling the Role Of Type I And Ii Interferons In Stat3-med...mentioning

confidence: 99%

“…While STAT3 is also activated during Type I IFN stimulation, it can also negatively regulate Type I IFN responses 144 . STAT3 signaling may also hinder the production of Type I IFNs, as recent evidence suggests that Type I IFN production increases when STAT3 is unphosphorylated 145 . As such STAT3 has a dual inhibitory role, where it acts to both suppress Type I IFN‐mediated signaling and lowers its production.…”

Section: Introductionmentioning

confidence: 99%

Metabolic adaptations determine whether natural killer cells fail or thrive within the tumor microenvironment

Moinuddin,

Poznanski,

Portillo

et al. 2024

Immunological Reviews

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SummaryNatural Killer (NK) cells are a top contender in the development of adoptive cell therapies for cancer due to their diverse antitumor functions and ability to restrict their activation against nonmalignant cells. Despite their success in hematologic malignancies, NK cell‐based therapies have been limited in the context of solid tumors. Tumor cells undergo various metabolic adaptations to sustain the immense energy demands that are needed to support their rapid and uncontrolled proliferation. As a result, the tumor microenvironment (TME) is depleted of nutrients needed to fuel immune cell activity and contains several immunosuppressive metabolites that hinder NK cell antitumor functions. Further, we now know that NK cell metabolic status is a main determining factor of their effector functions. Hence, the ability of NK cells to withstand and adapt to these metabolically hostile conditions is imperative for effective and sustained antitumor activity in the TME. With this in mind, we review the consequences of metabolic hostility in the TME on NK cell metabolism and function. We also discuss tumor‐like metabolic programs in NK cell induced by STAT3‐mediated expansion that adapt NK cells to thrive in the TME. Finally, we examine how other approaches can be applied to enhance NK cell metabolism in tumors.

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KLF4 Induces Colorectal Cancer by Promoting EMT via STAT3 Activation

Yuan,

Meng,

Xiang

2024

Dig Dis Sci

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STAT3 regulates antiviral immunity by suppressing excessive interferon signaling

Cited by 8 publications

References 57 publications

Spleen tyrosine kinase inhibitor R406 has both antiviral and anti‐inflammatory effects on severe influenza A infection

Spleen tyrosine kinase inhibitor R406 has both antiviral and anti‐inflammatory effects on severe influenza A infection

Metabolic adaptations determine whether natural killer cells fail or thrive within the tumor microenvironment

KLF4 Induces Colorectal Cancer by Promoting EMT via STAT3 Activation

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