ArticleScience translational medicine2016
Autoimmune manifestations in aged mice arise from early-life immune dysregulation.
Article in Science translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 51 citations in OpenAlex.
- Early-life adversity and negative emotional responses are associated with hashimoto's thyroiditis.Journal of endocrinological investigation · 2026Article
- Revisiting the CD40-CD40L axis: from mechanistic insight to therapeutic renewal in autoimmune disease.Current opinion in rheumatology · 2026Review
- Chest muscle area, spleen density, CD4 + T%, and C4 to predict the development of interstitial lung disease in patients with Sjögren's syndrome: a clinical prediction model.Clinical rheumatology · 2026Article
- Regulating the regulators via targeting CD38 in the tumor microenvironment.Frontiers in immunology · 2026Review
- Evaluating Anti-CCL25 as a Therapeutic Strategy to Disrupt Foci Formation in a Spontaneous Murine Model of Sjögren's Disease.International journal of molecular sciences · 2025Article
- Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders.Signal transduction and targeted therapy · 2024Review
- Inhibitory Effects of Extracellular Vesicles from iPS-Cell-Derived Mesenchymal Stem Cells on the Onset of Sialadenitis in Sjögren's Syndrome Are Mediated by Immunomodulatory Splenocytes and Improved by Inhibiting miR-125b.International journal of molecular sciences · 2023Article
- Sex-specific differences in primary Sjögren's disease.Frontiers in dental medicine · 2023Review
- The Future of Targeted Treatment of Primary Sjögren's Syndrome: A Focus on Extra-Glandular Pathology.International journal of molecular sciences · 2022Review
- Early Dry Eye Disease Onset in a NOD.H-2h4 Mouse Model of Sjögren's Syndrome.Investigative ophthalmology & visual science · 2022Article
- Novel Functions of Integrins as Receptors of CD154: Their Role in Inflammation and Apoptosis.Cells · 2022Review
- What Do We Know about the Microbiome in Cystic Fibrosis? Is There a Role for Probiotics and Prebiotics?Nutrients · 2022Review
- Tear miRNAs Identified in a Murine Model of Sjögren's Syndrome as Potential Diagnostic Biomarkers and Indicators of Disease Mechanism.Frontiers in immunology · 2022Article
- 29 mJournal of immunology research · 2022Article
- Current experimental methods to investigate the impact of specialized pro-resolving lipid mediators on Sjögren's syndrome.Frontiers in immunology · 2022Review
- Leveraging diet to engineer the gut microbiome.Nature reviews. Gastroenterology & hepatology · 2021Review
- Tissue-specific activation of Myd88-dependent pathways governs disease severity in primary Sjögren's syndrome.Journal of autoimmunity · 2021Article
- The enhanced immunopharmacology of VIB4920, a novel Tn3 fusion protein and CD40L antagonist, and assessment of its safety profile in cynomolgus monkeys.British journal of pharmacology · 2020Article
- Treatment with a CD40 Antagonist Antibody Reverses Severe Proteinuria and Loss of Saliva Production and Restores Glomerular Morphology in Murine Systemic Lupus Erythematosus.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- To reflect human autoimmune thyroiditis, thyroid peroxidase (not thyroglobulin) antibodies should be measured in female (not sex-independent) NOD.H2Clinical and experimental immunology · 2019Article
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
Abstract
Autoantibodies can be present years to decades before the onset of disease manifestations in autoimmunity. This finding suggests that the initial autoimmune trigger involves a peripheral lymphoid component, which ultimately drives disease pathology in local tissues later in life. We show that Sjögren's syndrome manifestations that develop in aged NOD.H-2h4 mice were driven by and dependent on peripheral dysregulation that arose in early life. Specifically, elimination of spontaneous germinal centers in spleens of young NOD.H-2h4 mice by transient blockade of CD40 ligand (CD40L) or splenectomy abolished Sjögren's pathology of aged mice. Strikingly, a single injection of anti-CD40L at 4 weeks of age prevented tertiary follicle neogenesis and greatly blunted the formation of key autoantibodies implicated in glandular pathology, including anti-muscarinic receptor antibodies. Microarray profiling of the salivary gland characterized the expression pattern of genes that increased with disease progression and showed that early anti-CD40L greatly repressed B cell function while having a broader effect on multiple biological pathways, including interleukin-12 and interferon signaling. A single prophylactic treatment with anti-CD40L also inhibited the development of autoimmune thyroiditis and diabetes in NOD.H-2h4 and nonobese diabetic mice, respectively, supporting a key role for CD40L in the pathophysiology of several autoimmune models. These results strongly suggest that early peripheral immune dysregulation gives rise to autoimmune manifestations later in life, and for diseases predated by autoantibodies, early prophylactic intervention with biologics may prove efficacious.
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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.