ArticleThe Journal of biological chemistry2013
Galectin-9 protein is up-regulated in astrocytes by tumor necrosis factor and promotes encephalitogenic T-cell apoptosis.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Association between Galectin Levels and Neurodegenerative Diseases: Systematic Review and Meta-Analysis.Biomolecules · 2022Pooled it
- Astrocyte-driven immunosuppression in the brain tumor microenvironment.Nature immunology · 2026Review
- Soluble TIM-3 and galectin-9 in cerebrospinal fluid are associated with disability at 6 months in aquaporin-4 IgG-positive neuromyelitis optica spectrum disorder.Frontiers in immunology · 2026Article
- Biomarkers of progressive multiple sclerosis decrease following autologous hematopoietic stem cell transplantation.Journal of neuroinflammation · 2025Article
- Sweet Aging: Glycocalyx and Galectins in CNS Aging and Neurodegenerative Disorders.International journal of molecular sciences · 2025Review
- PRP as a modulator of inflammation in FLS of RA patients by regulation of galectins and TGF-β1.Heliyon · 2024Article
- Astrocytes phenomics as new druggable targets in healthy aging and Alzheimer's disease progression.Frontiers in cellular neuroscience · 2024Review
- Monocyte-derived Galectin-9 and PD-L1 differentially impair adaptive and innate immune response in chronic HBV infection and their expression remain unaltered after antiviral therapy.Frontiers in immunology · 2024Article
- Influenza A virus infection disrupts oligodendrocyte homeostasis and alters the myelin lipidome in the adult mouse.Journal of neuroinflammation · 2023Article
- iAstrocytes do not restrain T cell proliferation in vitro.BMC neuroscience · 2023Article
- Establishment and verification of a nomogram and a preliminary study on predicting the clinical response of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in rheumatoid arthritis patients.Annals of translational medicine · 2022Article
- Role of CD8BMC emergency medicine · 2022Observational
- Galectins-Potential Therapeutic Targets for Neurodegenerative Disorders.International journal of molecular sciences · 2022Review
- Astrocyte Reaction to Catechol-Induced Cytotoxicity Relies on the Contact with Microglia Before Isolation.Neurotoxicity research · 2022Article
- Obesity-induced galectin-9 is a therapeutic target in B-cell acute lymphoblastic leukemia.Nature communications · 2022Article
- Galectin-9/Tim-3 pathway mediates dopaminergic neurodegeneration in MPTP-induced mouse model of Parkinson's disease.Frontiers in molecular neuroscience · 2022Article
- Covid-19 and oral diseases: Crosstalk, synergy or association?Reviews in medical virology · 2021Review
- Astrocytes in Multiple Sclerosis-Essential Constituents with Diverse Multifaceted Functions.International journal of molecular sciences · 2021Review
- The presence of TIM-3 positive cells in WHO grade III and IV astrocytic gliomas correlates with isocitrate dehydrogenase mutation status.Brain pathology (Zurich, Switzerland) · 2021Article
- Galectins - Important players of the immune response to CNS parasitic infection.Brain, behavior, & immunity - health · 2021Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Demyelination and axonal damage in multiple sclerosis (MS) are thought to be a consequence of inflammatory processes that are perpetuated by activated glia and infiltrating leukocytes. Galectin-9 is a β-galactoside binding lectin capable of modulating immune responses and appears to be up-regulated in MS. However, its role in the pathogenesis of MS has yet to be determined. Here, we report that proinflammatory cytokines induce galectin-9 (Gal-9) expression in primary astrocytes and the mechanism by which TNF up-regulates Gal-9. Astrocytes did not express Gal-9 under basal conditions nor did IL-6, IL-10, or IL-13 trigger Gal-9 expression. In contrast, IL-1β, IFN-γ, and particularly TNF up-regulated Gal-9 in astrocytes. TNF-induced Gal-9 expression was dependent on TNF receptor 1 (TNFR1) as TNF failed to induce Gal-9 in TNFR1(-/-) astrocytes. Blockade of the JNK MAP kinase pathway with the JNK inhibitor SP600125 abrogated TNF-induced Gal-9, whereas p38 and MEK inhibitors had minimal effects. Furthermore, specific knockdown of c-Jun via siRNA in astrocytes before TNF treatment greatly suppressed Gal-9 transcription, suggesting that TNF induces astroglial Gal-9 through the TNF/TNFR1/JNK/cJun signaling pathway. Finally, utilizing astrocytes from Lgals9 mutant (Gal-9(-/-)) mice as well as a myelin basic protein-specific Tim-3(+) encephalitogenic T-cell clone (LCN-8), we found that conditioned medium from TNF-stimulated Gal-9(+/+) but not Gal-9(-/-) astrocytes increased the percentage of apoptotic encephalitogenic T-cells. Together, our results suggest that Gal-9 is induced in astrocytes by TNF via the JNK/c-Jun pathway and that astrocyte-derived Gal-9 may function as an immunoregulatory protein in response to ongoing neuroinflammation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.