ArticleInvestigative ophthalmology & visual science2009
Orbital fibroblasts from patients with thyroid-associated ophthalmopathy overexpress CD40: CD154 hyperinduces IL-6, IL-8, and MCP-1.
Article in Investigative ophthalmology & visual science, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
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Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 162 citations in OpenAlex.
- Combined glucocorticoids and cyclophosphamide in the treatment of Graves' ophthalmopathy: a systematic review and meta-analysis.BMC endocrine disorders · 2024Pooled it
- Exploring tear fluid biomarkers and the ocular surface in thyroid eye disease.Acta ophthalmologica · 2026Article
- Gypenosides attenuate HAmerican journal of translational research · 2026Article
- PDGFRαAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Quantitative lipidomic analysis reveals distinct metabolic traits between stromal cell subpopulations in human orbital adipose tissue.Metabolism open · 2025Article
- Molecular pathway and mechanism responsible for the progress of thyroid-associated orbitopathy.International ophthalmology · 2025Review
- Nicotinamide N-Methyltransferase in the Inflammatory Pathogenesis of Graves' Orbitopathy.Investigative ophthalmology & visual science · 2025Article
- Genetic and Plasma Proteomic Approaches to Identify Therapeutic Targets for Graves' Disease and Graves' Ophthalmopathy.ImmunoTargets and therapy · 2025Article
- New Clues to the Pathogenesis of Idiopathic Orbital Inflammation: Elevated IL-8 and MCP-1 in Tear Fluid.Journal of ophthalmology · 2025Article
- Targeted immunotherapies for Graves' thyroidal & orbital diseases.Frontiers in immunology · 2025Review
- Review
- Peripheral CD3Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024Article
- Plasma exosomes from patients with active thyroid-associated orbitopathy induce inflammation and fibrosis in orbital fibroblasts.Journal of translational medicine · 2024Article
- Smoking enhances proliferation, inflammatory markers, and immunoglobulins in peripheral blood mononuclear cells from Graves' patients.Endocrine connections · 2024Article
- Article
- Extreme Tolerance of Extraocular Muscles to Diseases and Aging: Why and How?International journal of molecular sciences · 2024Review
- CD169iScience · 2024Article
- SOX9 Induces Orbital Fibroblast Activation in Thyroid Eye Disease Via MAPK/ERK1/2 Pathway.Investigative ophthalmology & visual science · 2024Article
- Immune checkpoints: new insights into the pathogenesis of thyroid eye disease.Frontiers in immunology · 2024Review
- Immunological Processes in the Orbit and Indications for Current and Potential Drug Targets.Journal of clinical medicine · 2023Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
purposeFibroblast diversity represents an emerging concept critical to our understanding of tissue inflammation, repair, and remodeling. Orbital fibroblasts heterogeneously display Thy-1 and exhibit unique phenotypic attributes that may explain the susceptibility of the human orbit to thyroid-associated ophthalmopathy (TAO). In the present study the authors investigated the role of CD40 ligation on macrophage chemoattractant protein-1 (MCP-1), IL-6, and IL-8 expression in fibroblasts from patients with TAO.
methodsHuman orbital fibroblasts were cultured from tissues obtained with informed consent from patients with TAO and from patients undergoing surgery for other noninflammatory conditions. The fibroblasts were then examined by flow cytometry, microscopy, and cytokine assays.
resultsThe authors report that orbital fibroblasts from patients with TAO expressed elevated levels of CD40. Surface CD40 could be further upregulated by IFN-gamma in TAO and control fibroblasts. This upregulation was mediated through Jak2 and could be blocked by dexamethasone and AG490, a powerful and specific inhibitor of tyrosine kinase. Treatment with CD154, the ligand for CD40, upregulated the expression of IL-6, IL-8, and MCP-1 in TAO fibroblasts but failed to do so in control cultures. Thy-1(+) fibroblasts displayed higher CD40 levels than did their Thy-1(-) counterparts and were largely responsible for this cytokine production. IL-1beta also induced MCP-1, IL-6, and IL-8 more vigorously in TAO-derived fibroblasts.
conclusionsCharacterization of orbital fibroblasts and their differential expression of cytokines and receptors should prove invaluable in understanding the site-specific nature of TAO and the development of specific therapies.
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