Article
Immunology
Feiyu Fu, Zhenyu Lin, Yanlin Li, Jie Wang, Yawen Li, Pengcheng Liu, Zhaofei Wang, Jingjiao Ma, Yaxian Yan, Jianhe Sun, Yuqiang Cheng
Summary: This study cloned and analyzed the molecular characteristics of goose STING (GoSTING). The results showed that GoSTING plays a crucial role in the regulation of RNA virus replication and is a key component of the innate immune defense in geese.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Chih-Hang Anthony Tang, Avery C. Lee, Shiun Chang, Qin Xu, Andong Shao, Yun Lo, Walker T. Spalek, Javier A. Pinilla-Ibarz, Juan R. Del Valle, Chih-Chi Andrew Hu
Summary: STING plays a role in negatively regulating BCR signaling in B cells, leading to reduced response to BCR activation; both expression level and deficiency of STING can impact B cell function and antigen response.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Oncology
Xiaomei Zhao, Biao Wang, Yuan Zhuang, Shisuo Du, Zhaochong Zeng
Summary: This study investigates the immunomodulatory effects of different dose-fractionation schedules and finds that a single high-dose radiation schedule has a stronger antitumor effect. The study also reveals the involvement of the cGAS/STING signaling pathway in the immunomodulatory effects of single high-dose radiation.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2023)
Article
Medicine, Research & Experimental
Zhilin Hu, Xiaoyan Yu, Rui Ding, Ben Liu, Chuanjia Gu, Xiu-Wu Pan, Qiaoqiao Han, Yuerong Zhang, Jie Wan, Xin-Gang Cui, Jiayuan Sun, Qiang Zou
Summary: Activation of STING signaling in DCs is enhanced by glycolysis, leading to increased antitumor immunity. Tumor-infiltrating DCs exhibit elevated glycolytic activity, and blocking glycolysis impairs antitumor immunity. Mechanistically, glycolysis enhances ATP production, boosting STING activation and DC-mediated antitumor functions. Additionally, DC-intrinsic STING activation accelerates HIF-1 alpha-mediated glycolysis, establishing a positive feedback loop. Importantly, glycolysis facilitates STING-dependent DC activity in tissue samples from patients with non-small cell lung cancer. These findings provide insights into the crosstalk between glycolytic metabolism and STING signaling, offering potential for improving cancer therapies.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Microbiology
Lin Lv, Li Chai, Jie Wang, Mengge Wang, Danhui Qin, Hui Song, Yue Fu, Chunyuan Zhao, Jihui Jia, Wei Zhao, Mutian Jia
Summary: In this study, we identified a transmembrane selenoprotein, SELENOK, located in the endoplasmic reticulum (ER), which is induced during viral infection and enhances innate immune response against herpes simplex virus-1 (HSV-1) by promoting STING oligomerization. SELENOK interacts with STING, facilitating its translocation from the ER to the Golgi. Thus, controlling STING activation through selenium-mediated SELENOK expression could be a potential therapeutic strategy for STING-associated diseases.
Review
Cell Biology
Chen Chen, Pinglong Xu
Summary: cGAS-STING signaling pathway plays multiple roles at the cellular level and impacts disease pathogenesis. Understanding the mechanisms by which DNA sensing triggers these cellular processes is a pressing challenge.
TRENDS IN CELL BIOLOGY
(2023)
Article
Immunology
Lingqi Kong, Wenyu Li, E. Chang, Wuxuan Wang, Nan Shen, Xiang Xu, Xinyue Wang, Yan Zhang, Wen Sun, Wei Hu, Pengfei Xu, Xinfeng Liu
Summary: This study demonstrates that STING, activated by mtDNA, promotes microglial polarization towards the M1 phenotype following ischemic stroke. Inhibition of STING may serve as a potential therapeutic strategy to mitigate neuroinflammation and improve stroke outcomes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Yewei Ji, Yuan Luo, Yating Wu, Yao Sun, Lianfeng Zhao, Zhen Xue, Mengqi Sun, Xiaoqiong Wei, Zinan He, Shuangcheng Alivia Wu, Liangguang Leo Lin, You Lu, Lei Chang, Fei Chen, Siyu Chen, Wei Qian, Xiaoxi Xu, Shengnuo Chen, Dongli Pan, Zhangsen Zhou, Sheng Xia, Chih-Chi Andrew Hu, Tingbo Liang, Ling Qi
Summary: The SEL1L-HRD1 complex regulates STING protein levels in the endoplasmic reticulum and negatively regulates its activation. SEL1L-HRD1 deficiency amplifies STING signaling in macrophages and enhances immunity against viral infection and tumor growth. This study identifies a key role of SEL1L-HRD1 ERAD in innate immunity and provides a therapeutic approach for targeting STING.
NATURE CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Weijie Ouyang, Shoubi Wang, Dan Yan, Jieli Wu, Yunuo Zhang, Wei Li, Jiaoyue Hu, Zuguo Liu
Summary: By studying dry eye models and patient samples, as well as conducting cellular experiments, it was found that under stress, mitochondrial DNA can activate the cGAS-STING pathway and exacerbate inflammation and damage to the ocular surface. Inhibiting this pathway can reduce inflammatory responses. This study revealed a new mechanism by which ocular surface diseases respond to environmental stress.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Immunology
Tong Li, Seoyun Yum, Minghao Li, Xiang Chen, Xiaoxia Zuo, Zhijian J. Chen
Summary: Defective DNA clearance in DNase II-/- mice leads to lethal inflammatory diseases that can be rescued by deleting cGAS or STING. The study found that distinct signaling pathways downstream of STING play different roles in disease manifestation, with TBK1 recruitment to STING mediating autoinflammatory arthritis caused by DNase II deficiency. This discovery may provide new insights into therapeutic strategies for certain autoinflammatory diseases.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Jiawen Zhang, Yunfei Chen, Xianfei Chen, Wen Zhang, Linlin Zhao, Linjun Weng, Hongling Tian, Zhiqiang Wu, Xiao Tan, Xin Ge, Ping Wang, Lan Fang
Summary: The study identified that elevated USP35 levels in ovarian cancer correlate with reduced CD8(+) T cell infiltration and poor prognosis in patients. Silencing USP35 enhances STING activity, increases type I interferon expression, and directly deubiquitinates and inactivates STING. Furthermore, USP35 sensitizes ovarian cancer cells to DNA-damage chemotherapeutic drug cisplatin, suggesting its potential as a therapeutic target for ovarian cancer.
CELL DEATH AND DIFFERENTIATION
(2021)
Review
Immunology
Isabelle Couillin, Nicolas Riteau
Summary: Innate immunity is maintained by a set of evolutionarily conserved receptors that finely probe the local environment and maintain host integrity. Recent literature demonstrates that self-nucleic acid detection through the STING pathway plays a central role in various processes, from cell physiology to inflammatory diseases, autoimmunity, and cancer. The cGAS/STING pathway is involved in inflammatory diseases, neurodegenerative conditions, and cancer, connecting various cell processes including autophagy and cell death.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Devon Jeltema, Kennady Abbott, Nan Yan
Summary: STING signaling plays a central role in multiple autoinflammatory and neurodegenerative diseases. This study reviews the influence of STING trafficking on signaling, proposes a model of tonic STING signaling, and discusses the emerging link between dysregulated STING trafficking and neurodegenerative disease.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Review
Pharmacology & Pharmacy
Patrick Kwabena Oduro, Xianxian Zheng, Jinna Wei, Yanze Yang, Yuefei Wang, Han Zhang, Erwei Liu, Xiumei Gao, Mei Du, Qilong Wang
Summary: The cGAS-STING signaling pathway is closely related to cardiovascular and metabolic disorders and plays an important regulatory role in various sterile inflammatory diseases. Studying this signaling pathway is of great significance for understanding the relationship between cardiovascular and metabolic tissues and diseases.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Multidisciplinary Sciences
Yaling Dou, Rui Chen, Siyao Liu, Yi-Tsang Lee, Ji Jing, Xiaoxuan Liu, Yuepeng Ke, Rui Wang, Yubin Zhou, Yun Huang
Summary: The study introduces a light-sensitive optogenetic device, LiSmore, to remotely modulate the cGAS/STING signaling pathway and enhance immune response. The authors demonstrate that LiSmore can boost antitumor immunity and improve the efficacy of immune checkpoint blockade in mice.
NATURE COMMUNICATIONS
(2023)
Article
Rheumatology
M. A. Nielsen, D. Koster, S. Greisen, A. Troldborg, K. Stengaard-Pedersen, P. Junker, K. Horslev-Petersen, M. L. Hetland, M. Ostergaard, M. Hvid, H. Leffler, T. W. Kragstrup, B. Deleuran
Summary: The study found that patients with rheumatoid arthritis (RA) had persistently increased levels of galectin-3 (Gal-3) in their plasma, and changes in Gal-3 levels were associated with long-term disease activity. Gal-3 levels in synovial fluid were also significantly elevated. In vitro experiments showed that a Gal-3 inhibitor could reduce the activity of inflammatory cells.
SCANDINAVIAN JOURNAL OF RHEUMATOLOGY
(2023)
Article
Rheumatology
Christian Ammitzboll, Marianne Kragh Thomsen, Jakob Bogh Andersen, Lars Erik Bartels, Marie-Louise From Hermansen, Anders Dahl Johannsen, Clara Elbaek Mistegaard, Susan Mikkelsen, Signe Risbol Vils, Christian Erikstrup, Ellen-Margrethe Hauge, Anne Troldborg
Summary: This study investigated the effect of a two-dose mRNA vaccine on patients with systemic lupus erythematosus or rheumatoid arthritis. The results showed that the vaccine effectively increased patients' antibody levels against SARS-CoV-2 and reduced their fear of COVID-19. However, the use of rituximab, prednisone, and methotrexate had a negative impact on the vaccine response.
MODERN RHEUMATOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Anthony Vial, Luca Costa, Patrice Dosset, Pietro Rosso, Gaelle Boutieres, Orestis Faklaris, Heiko Haschke, Pierre-Emmanuel Milhiet, Christine M. Doucet
Summary: Nuclear pore complexes (NPCs) are the gateways that control molecular transport between the nucleus and cytoplasm in eukaryotic cells. Recent studies have revealed the arrangement of most constituents in human NPCs using cryo-EM and AI-based protein modeling. However, the structure of the basket, which caps the nucleoplasmic side of the pore, remains poorly resolved. Using atomic force microscopy (AFM) and single molecule localization microscopy (SMLM), researchers discovered that the basket is highly flexible and can adopt different conformations, allowing diverse cargoes to pass through NPCs.
Article
Multidisciplinary Sciences
Tim Vierbuchen, Shiuli Agarwal, John L. Johnson, Liraz Galia, Xuqiu Lei, Karina Stein, David Olagnier, Karoline Gaede, Christian Herzmann, Christian K. Holm, Holger Heine, Athma Pai, Aisling O'Hara Hall, Kasper Hoebe, Katherine A. Fitzgerald
Summary: The long non-coding RNA LUCAT1 is a negative feedback regulator of interferon and cytokine expression in human myeloid cells. It binds to proteins involved in mRNA processing and alternative splicing, and its absence leads to altered splicing and reduced expression of the NR4A2 gene, resulting in elevated immune gene expression. Furthermore, elevated LUCAT1 levels are found in patients with inflammatory bowel disease, asthma, and chronic obstructive pulmonary disease, suggesting its role in the regulation of inflammatory diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Rheumatology
Christian Ammitzboll, Marianne Kragh Thomsen, Jakob Bogh Andersen, Jens Magnus Berth Jensen, Marie-Louise From Hermansen, Anders Dahl Johannsen, Mads Lamm Larsen, Clara Elbaek Mistegaard, Susan Mikkelsen, Fruzsina Szabados, Signe Risbol Vils, Christian Erikstrup, Ellen-Margrethe Hauge, Anne Troldborg
Summary: This study aimed to investigate the effect of either a booster vaccine or revaccination on the antibody response to COVID-19 mRNA vaccines in rheumatic disease patients treated with rituximab. The study found that most patients had impaired humoral response after the booster dose or revaccination, and approximately one-third of the patients showed seroconversion. Measurable B cells before boosting or revaccination were the strongest predictor of antibody response.
Article
Virology
Frederik Holm Rothemejer, Nanna Pi Lauritsen, Anna Karina Juhl, Mariane Hogsbjerg Schleimann, Saskia Konig, Ole Schmeltz Sogaard, Rasmus O. Bak, Martin Tolstrup
Summary: This study demonstrates the development of HIV-resistant CAR T cells using CRISPR/Cas9 targeted integration of a CAR cassette into the CCR5 locus. The anti-HIV CAR T cells showed specific lysis of HIV-infected cells in vitro and transiently limited HIV infection in a PBMC humanized mouse model of HIV infection.
Article
Oncology
Eileen Wedge, Ulvi Ahmadov, Thomas B. Hansen, Zongliang Gao, Morten Tulstrup, Christophe Come, Sridhar Nonavinkere Srivatsan, Tanzir Ahmed, Jakob S. Jespersen, Balthasar C. Schlotmann, Claudia Schollkopf, Klas Raaschou-Jensen, Niels Odum, Jorgen Kjems, Rasmus O. Bak, Matthew J. Walter, Kirsten Gronbaek, Lasse S. Kristensen
Summary: Mutations in the U2AF1 gene are associated with a higher occurrence of myelodysplastic neoplasms (MDS) and a worse prognosis, but the exact molecular mechanisms are not fully understood. This study found that U2AF1 mutations may impact circRNA production, leading to increased cancer development. Increased circRNA expression levels were observed in cells and patient samples with U2AF1 mutations, suggesting a potential role of circRNA as a biomarker and therapeutic target in MDS.
Article
Biology
Shangchen Yang, Tianming Lan, Rongping Wei, Ling Zhang, Lin Lin, Hanyu Du, Yunting Huang, Guiquan Zhang, Shan Huang, Minhui Shi, Chengdong Wang, Qing Wang, Rengui Li, Lei Han, Dan Tang, Haimeng Li, Hemin Zhang, Jie Cui, Haorong Lu, Jinrong Huang, Yonglun Luo, Desheng Li, Qiu-Hong Wan, Huan Liu, Sheng-Guo Fang
Summary: This study provides insights into the cellular basis and transcriptomic regulatory clues for the low metabolism in giant pandas, and helps to understand the physiological adaptation response to low nutrient conditions.
Article
Oncology
Justin V. Joseph, Mathilde S. Blaavand, Huiqiang Cai, Fabienne Vernejoul, Rasmus W. Knopper, Thomas B. Lindhardt, Kristian A. Skipper, Esben Axelgaard, Line Reinert, Jacob G. Mikkelsen, Per Borghammer, Soren E. Degn, Eric Perouzel, Henrik Hager, Brian Hansen, Joanna M. Kalucka, Mikkel Vendelbo, Soren R. Paludan, Martin K. Thomsen
Summary: This study focused on glioblastoma and investigated the activation of the innate immune system through long-term STING activation as a potential treatment approach. The results showed that this approach reduced tumor progression and prolonged survival. Additionally, prolonged STING activation led to alterations in tumor vasculature and activation of VEGFR. Combination treatment with anti-PD1 did not provide any additional benefits, suggesting that STING activation alone is sufficient to hinder tumor development.
Article
Immunology
Mads Lamm Larsen, Anne Troldborg, Erik J. M. Toonen, Lisa Hurler, Zoltan Prohaszka, Laszlo Cervenak, Annette Gudmann Hansen, Steffen Thiel
Summary: This study aims to differentiate between classical or lectin pathway-mediated complement activation in SLE patients by quantifying pathway-specific protein complexes. The classical pathway is activated in active SLE disease, whereas activation of the lectin pathway might be more specific to disease manifestations like lupus nephritis.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Louise Dalskov, Hans Henrik Gad, Rune Hartmann
Summary: Interferons are antiviral cytokines that are essential in the innate immune response to viral infections. They are produced and released by cells in response to viral stimuli, and induce the transcription of numerous genes in neighboring cells. These gene products either directly combat the viral infection or contribute to shaping the immune response.
Article
Biochemistry & Molecular Biology
Fanghui Ren, Ryo Narita, Ahmad S. Rashidi, Stefanie Fruhwurth, Zongliang Gao, Rasmus O. Bak, Martin K. Thomsen, Georges M. G. M. Verjans, Line S. Reinert, Soren R. Paludan
Summary: Neurotropic viruses such as herpes simplex virus (HSV) can infect neurons and cause severe diseases. HSV-induced neuronal cell death is mediated by gasdermin E (GSDME) and involves endoplasmic reticulum stress, caspase activation, and mitochondria-dependent apoptosis. The necrotic neurons release alarmins, triggering inflammatory responses in microglia.
Article
Multidisciplinary Sciences
Cecilia Fahlquist-Hagert, Thomas R. Wittenborn, Ewa Terczynska-Dyla, Kristian Savstrup Kastberg, Emily Yang, Alysa Nicole Rallistan, Quinton Raymond Markett, Gudrun Winther, Sofie Fonager, Lasse F. Voss, Mathias K. Pedersen, Nina van Campen, Alexey Ferapontov, Lisbeth Jensen, Jinrong Huang, John D. Nieland, Cees E. van der Poel, Johan Palmfeldt, Michael C. Carroll, Paul J. Utz, Yonglun Luo, Lin Lin, Soren E. Degn
Summary: Circumstantial evidence suggests that B cells may instruct T cells to break tolerance. A murine model experiment demonstrated that the autoimmune response can be initiated outside of germinal centers. B cells can directly relay autoreactivity between different compartments of MHC-restricted T cells and propagate the autoimmune response.
NATURE COMMUNICATIONS
(2023)
Review
Cell Biology
Nanna S. Mikkelsen, Rasmus O. Bak
Summary: Genome editing technologies have great potential for various applications, but they often suffer from low editing efficiencies. Enrichment strategies can help improve these technologies and their applications in research and therapy.
JOURNAL OF BIOMEDICAL SCIENCE
(2023)