ArticleInternational journal of molecular sciences2019
Galectin-9 Is a Possible Promoter of Immunopathology in Rheumatoid Arthritis by Activation of Peptidyl Arginine Deiminase 4 (PAD-4) in Granulocytes.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Galectin-9Aging cell · 2026Article
- The TIM-3/Gal-9 Pathway: A Promising Therapeutic Target for Regulation of Immune Checkpoint in Rheumatoid Arthritis.Current rheumatology reviews · 2026Review
- Differential Expression of Galectin-1 and Galectin-9 in Immune-Mediated Inflammatory Diseases.International journal of molecular sciences · 2025Article
- Galectin-9 treatment is cytotoxic for B cell lymphoma by disrupting autophagy.Frontiers in pharmacology · 2025Article
- Galectin-9 as an indicator of functional limitations and radiographic joint damage in patients with rheumatoid arthritis.Frontiers in immunology · 2024Article
- Targeting Neutrophil Extracellular Traps in Gouty Arthritis: Insights into Pathogenesis and Therapeutic Potential.Journal of inflammation research · 2024Review
- Review
- Advancing Treatment in Bullous Pemphigoid: A Comprehensive Review of Novel Therapeutic Targets and Approaches.Clinical reviews in allergy & immunology · 2023Review
- Galectin-9 has non-apoptotic cytotoxic activity toward acute myeloid leukemia independent of cytarabine resistance.Cell death discovery · 2023Article
- Selective inhibition of peptidyl-arginine deiminase (PAD): can it control multiple inflammatory disorders as a promising therapeutic strategy?Inflammopharmacology · 2023Review
- Article
- Peptidylarginine deiminase enzymes and citrullinated proteins in female reproductive physiology and associated diseases†.Biology of reproduction · 2022Review
- Galectin-9/Tim-3 pathway mediates dopaminergic neurodegeneration in MPTP-induced mouse model of Parkinson's disease.Frontiers in molecular neuroscience · 2022Article
- Galectin-9 Triggers Neutrophil-Mediated Anticancer Immunity.Biomedicines · 2021Article
- Neutrophils promote T-cell activation through the regulated release of CD44-bound Galectin-9 from the cell surface during HIV infection.PLoS biology · 2021Article
- Immunomodulator Galectin-9 is Increased in Blood and Skin of Patients with Bullous Pemphigoid.Acta dermato-venereologica · 2021Article
- Aberrantly Expressed Galectin-9 Is Involved in the Immunopathogenesis of Anti-MDA5-Positive Dermatomyositis-Associated Interstitial Lung Disease.Frontiers in cell and developmental biology · 2021Article
- Association between inflammatory cytokines and immune-checkpoint molecule in rheumatoid arthritis.PloS one · 2021Observational
- Differential regulation and correlation between galectin-9 and anti-CCP antibody (ACPA) in rheumatoid arthritis patients.Arthritis research & therapy · 2020Observational
- Excessive Neutrophils and Neutrophil Extracellular Traps in COVID-19.Frontiers in immunology · 2020Article
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
The aetiology of rheumatoid arthritis (RA) is unknown, but citrullination of proteins is thought to be an initiating event. In addition, it is increasingly evident that the lung can be a potential site for the generation of autoimmune triggers before the development of joint disease. Here, we identified that serum levels of galectin-9 (Gal-9), a pleiotropic immunomodulatory protein, are elevated in RA patients, and are even further increased in patients with comorbid bronchiectasis, a lung disease caused by chronic inflammation. The serum concentrations of Gal-9 correlate with C-reactive protein levels and DAS-28 score. Gal-9 activated polymorphonuclear leukocytes (granulocytes) in vitro, which was characterized by increased cytokine secretion, migration, and survival. Further, granulocytes treated with Gal-9 upregulated expression of peptidyl arginine deiminase 4 (PAD-4), a key enzyme required for RA-associated citrullination of proteins. Correspondingly, treatment with Gal-9 triggered citrullination of intracellular granulocyte proteins that are known contributors to RA pathogenesis (i.e., myeloperoxidase, alpha-enolase, MMP-9, lactoferrin). In conclusion, this study identifies for the first time an immunomodulatory protein, Gal-9, that triggers activation of granulocytes leading to increased PAD-4 expression and generation of citrullinated autoantigens. This pathway may represent a potentially important mechanism for development of RA.
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