ArticleArthritis research & therapy2011
Lymphotoxin-beta receptor blockade reduces CXCL13 in lacrimal glands and improves corneal integrity in the NOD model of Sjögren's syndrome.
Article in Arthritis research & therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Elevated CXCL13 in primary Sjögren's syndrome and its correlation with disease activity: a systematic review and meta-analysis.Clinical rheumatology · 2022Pooled it
- Clinical Efficacy and Safety of Baminercept, a Lymphotoxin β Receptor Fusion Protein, in Primary Sjögren's Syndrome: Results From a Phase II Randomized, Double-Blind, Placebo-Controlled Trial.Arthritis & rheumatology (Hoboken, N.J.) · 2018Trial
- Dynamic progression of ectopic lymphoid structure formation in lacrimal glands of a Sjögren's disease murine model.Frontiers in immunology · 2026Article
- Targeting high endothelial venules: potential strategies for cancer treatment.Annals of medicine · 2025Review
- Regulatory T cell and endothelial cell crosstalk.Nature reviews. Immunology · 2025Review
- Salivary gland transcriptomic analysis and immunophenotyping in the IL-14α transgenic mouse model of Sjögren's disease.Frontiers in dental medicine · 2025Article
- Review
- Functionally diverse thymic medullary epithelial cells interplay to direct central tolerance.Cell reports · 2024Article
- Investigative biological therapies for primary Sjögren's syndrome.Archives of medical science : AMS · 2024Article
- Chemokines and lymphocyte homing in Sjögren's syndrome.Frontiers in immunology · 2024Review
- Distinct fibroblast functions associated with fibrotic and immune-mediated inflammatory diseases and their implications for therapeutic development.F1000Research · 2024Review
- Ectopic lymphoid structures in the aged lacrimal glands.Clinical immunology (Orlando, Fla.) · 2023Article
- Tertiary lymphoid structures in autoimmune diseases.Frontiers in immunology · 2023Review
- The role of microRNAs involved in the disorder of blood-brain barrier in the pathogenesis of multiple sclerosis.Frontiers in immunology · 2023Review
- Role of lymphotoxin alpha as a new molecular biomarker in revolutionizing tear diagnostic testing for dry eye disease.International journal of ophthalmology · 2023Review
- The emerging role of regulatory cell-based therapy in autoimmune disease.Frontiers in immunology · 2022Review
- Role of the CXCL13/CXCR5 Axis in Autoimmune Diseases.Frontiers in immunology · 2022Review
- High endothelial venules (HEVs) in immunity, inflammation and cancer.Angiogenesis · 2021Review
- Targeted Therapy for Primary Sjögren's Syndrome: Where are We Now?BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021Review
- HES5-mediated repression of LIGHT transcription may contribute to apoptosis in hepatocytes.Cell death discovery · 2021Article
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionIn Sjögren's syndrome, keratoconjunctivitis sicca (dry eye) is associated with infiltration of lacrimal glands by leukocytes and consequent losses of tear-fluid production and the integrity of the ocular surface. We investigated the effect of blockade of the lymphotoxin-beta receptor (LTBR) pathway on lacrimal-gland pathology in the NOD mouse model of Sjögren's syndrome.
methodsMale NOD mice were treated for up to ten weeks with an antagonist, LTBR-Ig, or control mouse antibody MOPC-21. Extra-orbital lacrimal glands were analyzed by immunohistochemistry for high endothelial venules (HEV), by Affymetrix gene-array analysis and real-time PCR for differential gene expression, and by ELISA for CXCL13 protein. Leukocytes from lacrimal glands were analyzed by flow-cytometry. Tear-fluid secretion-rates were measured and the integrity of the ocular surface was scored using slit-lamp microscopy and fluorescein isothiocyanate (FITC) staining. The chemokine CXCL13 was measured by ELISA in sera from Sjögren's syndrome patients (n = 27) and healthy controls (n = 30). Statistical analysis was by the two-tailed, unpaired T-test, or the Mann-Whitney-test for ocular integrity scores.
resultsLTBR blockade for eight weeks reduced B-cell accumulation (approximately 5-fold), eliminated HEV in lacrimal glands, and reduced the entry rate of lymphocytes into lacrimal glands. Affymetrix-chip analysis revealed numerous changes in mRNA expression due to LTBR blockade, including reduction of homeostatic chemokine expression. The reduction of CXCL13, CCL21, CCL19 mRNA and the HEV-associated gene GLYCAM-1 was confirmed by PCR analysis. CXCL13 protein increased with disease progression in lacrimal-gland homogenates, but after LTBR blockade for 8 weeks, CXCL13 was reduced approximately 6-fold to 8.4 pg/mg (+/- 2.7) from 51 pg/mg (+/-5.3) in lacrimal glands of 16 week old control mice. Mice given LTBR blockade exhibited an approximately two-fold greater tear-fluid secretion than control mice (P = 0.001), and had a significantly improved ocular surface integrity score (P = 0.005). The mean CXCL13 concentration in sera from Sjögren's patients (n = 27) was 170 pg/ml, compared to 92.0 pg/ml for sera from (n = 30) healthy controls (P = 0.01).
conclusionsBlockade of LTBR pathways may have therapeutic potential for treatment of Sjögren's syndrome.
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