ArticlePloS one2012
Galectin-9 controls CD40 signaling through a Tim-3 independent mechanism and redirects the cytokine profile of pathogenic T cells in autoimmunity.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- New insights on Galectin-9 expression in cancer prognosis: An updated systemic review and meta-analysis.PloS one · 2025Pooled it
- Decreased galectin-9 and increased Tim-3 expression are related to poor prognosis in gastric cancer.PloS one · 2013Trial
- Galectin-9-An Emerging Glyco-Immune Checkpoint Target for Cancer Therapy.International journal of molecular sciences · 2025Review
- TIM-3/Galectin-9 Immune Axis in Colorectal Cancer in Relation to KRAS, NRAS, BRAF, PIK3CA, AKT1 Mutations, MSI Status, and the Cytokine Milieu.International journal of molecular sciences · 2025Article
- Multifaceted roles of Galectins: from carbohydrate binding to targeted cancer therapy.Biomarker research · 2025Review
- Galectin-9: diverse roles in skin disease.Frontiers in allergy · 2025Review
- Plasma galectin-9 relates to cognitive performance and inflammation among adolescents with vertically acquired HIV.AIDS (London, England) · 2024Article
- Revisiting Multi-Omics Data to Unravel Galectins as Prognostic Factors in Head and Neck Squamous Cell Carcinoma.Biomedicines · 2024Article
- Galectin-9 - ligand axis: an emerging therapeutic target for multiple myeloma.Frontiers in immunology · 2024Review
- A new emerging target in cancer immunotherapy: Galectin-9 (LGALS9).Genes & diseases · 2023Review
- Chimera and Tandem-Repeat Type Galectins: The New Targets for Cancer Immunotherapy.Biomolecules · 2023Review
- Regulatory Fibroblast-Like Synoviocytes Cell Membrane Coated Nanoparticles: A Novel Targeted Therapy for Rheumatoid Arthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Canine diabetes mellitus demonstrates multiple markers of chronic inflammation including Th40 cell increases and elevated systemic-immune inflammation index, consistent with autoimmune dysregulation.Frontiers in immunology · 2023Article
- Article
- Obesity-induced galectin-9 is a therapeutic target in B-cell acute lymphoblastic leukemia.Nature communications · 2022Article
- Review
- Exploring the Pathogenic Role and Therapeutic Implications of Interleukin 2 in Autoimmune Hepatitis.Digestive diseases and sciences · 2021Review
- The TIM3/Gal9 signaling pathway: An emerging target for cancer immunotherapy.Cancer letters · 2021Article
- Characterization of the First Genome of Porcine mastadenovirus B (HNU1 Strain) and Implications on Its Lymphoid and Special Origin.Virologica Sinica · 2020Article
- Down-regulation and Clinical Implication of Galectin-9 Levels in Patients with Acute Coronary Syndrome and Chronic Kidney Disease.Current medical science · 2020Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
While it has long been understood that CD40 plays a critical role in the etiology of autoimmunity, glycobiology is emerging as an important contributor. CD40 signaling is also gaining further interest in transplantation and cancer therapies. Work on CD40 signaling has focused on signaling outcomes and blocking of its ligand, CD154, while little is known about the actual receptor itself and its control. We demonstrated that CD40 is in fact several receptors occurring as constellations of differentially glycosylated forms of the protein that can sometimes form hybrid receptors with other proteins. An enticing area of autoimmunity is differential glycosylation of immune molecules leading to altered signaling. Galectins interact with carbohydrates on proteins to effect such signaling alterations. Studying autoimmune prone NOD and non-autoimmune BALB/c mice, here we reveal that in-vivo CD40 signals alter the glycosylation status of non-autoimmune derived CD4 T cells to resemble that of autoimmune derived CD4 T cells. Galectin-9 interacts with CD40 and, at higher concentrations, prevents CD40 induced proliferative responses of CD4(lo)CD40(+) effector T cells and induces cell death through a Tim-3 independent mechanism. Interestingly, galectin-9, at lower concentrations, alters the surface expression of CD3, CD4, and TCR, regulating access to those molecules and thereby redirects the inflammatory cytokine phenotype and CD3 induced proliferation of autoimmune CD4(lo)CD40(+) T cells. Understanding the dynamics of the CD40 receptor(s) and the impact of glycosylation status in immunity will gain insight into how to maintain useful CD40 signals while shutting down detrimental ones.
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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.