ArticleJCI insight2020
Thymic rejuvenation via FOXN1-reprogrammed embryonic fibroblasts (FREFs) to counteract age-related inflammation.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 36 citations in OpenAlex.
- Article
- Thymulin restrains age-associated myeloid inflammation and enhances cancer immunotherapy.Nature communications · 2026Article
- Clinical rationale for thymic restoration in adult immunosenescence.Immunity & ageing : I & A · 2026Review
- From Development to Aging: Dynamic Roles of the Thymic Medulla in T Cell Biology.Immunological reviews · 2026Review
- Molecular heterogeneity and differential metabolic signatures in thymic adipocytes.bioRxiv : the preprint server for biology · 2026Article
- Age-related thymic involution: Mechanistic insights and rejuvenating approaches to restore immune function.Science advances · 2026Review
- From molecular damage to regulatory constraint: epigenetic and metabolic limits of cellular plasticity in aging.Frontiers in aging · 2026Review
- Editorial: Thymus research and development: a new look at the past, current knowledge, and future perspectives.Frontiers in immunology · 2026Article
- Network-orchestrated regulation of thymic dysfunction and restoration.Frontiers in immunology · 2026Review
- HIV infection and immunosenescence: challenges and intervention strategies.BMC medicine · 2025Review
- Redox-Immune Axis and Ozone Pollution: From Oxidative Stress to Thymic Involution and Neurodegeneration.Medical sciences (Basel, Switzerland) · 2025Review
- Immunosenescence: signaling pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Age-Related Thymic Involution.Advances in experimental medicine and biology · 2025Review
- The pathophysiological mechanisms of immunosenescence in coronary artery disease.Frontiers in cell and developmental biology · 2025Review
- Immunosenescence and its related comorbidities in older people living with HIV.Infectious diseases & immunity · 2025Review
- Review
- Transcriptional profile of human thymus reveals IGFBP5 is correlated with age-related thymic involution.Frontiers in immunology · 2024Article
- Inflammaging, immunosenescence, and cardiovascular aging: insights into long COVID implications.Frontiers in cardiovascular medicine · 2024Review
- Foxn1 overexpression promotes thymic epithelial progenitor cell proliferation and mTEC maintenance, but does not prevent thymic involution.Development (Cambridge, England) · 2023Article
- Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases.Signal transduction and targeted therapy · 2023Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Age-associated systemic, chronic inflammation is partially attributed to increased self-autoreactivity, resulting from disruption of central tolerance in the aged, involuted thymus. This involution causally results from gradually decreased expression of the transcription factor FOXN1 in thymic epithelial cells (TECs), whereas exogenous FOXN1 in TECs can partially rescue age-related thymic involution. TECs induced from FOXN1-overexpressing embryonic fibroblasts can generate an ectopic de novo thymus under the kidney capsule, and intrathymic injection of naturally young TECs can lead to middle-aged thymus regrowth. Therefore, as a thymic rejuvenation strategy, we extended these 2 findings by combining them with 2 types of promoter-driven (Rosa26CreERT and FoxN1Cre) Cre-mediated FOXN1-reprogrammed embryonic fibroblasts (FREFs). We engrafted these FREFs directly into the aged murine thymus. We found substantial regrowth of the native aged thymus with rejuvenated architecture and function in both males and females, exhibiting increased thymopoiesis and reinforced thymocyte negative selection, along with reduced senescent T cells and autoreactive T cell-mediated inflammation in old mice. Therefore, this approach has preclinical significance and presents a strategy to potentially rescue decreased thymopoiesis and perturbed negative selection to substantially, albeit partially, restore defective central tolerance and reduce subclinical autoimmune symptoms in elderly people.
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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.