ArticlePLoS biology2017
Capacity of tTreg generation is not impaired in the atrophied thymus.
Article in PLoS biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 50 citations in OpenAlex.
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- Anthraquinones and Aloe Vera Extracts as Potential Modulators of Inflammaging Mechanisms: A Translational Approach from Autoimmune to Onco-Hematological Diseases.Molecules (Basel, Switzerland) · 2025Review
- Physiological and pathological roles of the thymus and value of thymectomy in myasthenia gravis: a narrative review.Mediastinum (Hong Kong, China) · 2024Review
- T cell aging and Alzheimer's disease.Frontiers in immunology · 2023Review
- From aging to long COVID: exploring the convergence of immunosenescence, inflammaging, and autoimmunity.Frontiers in immunology · 2023Review
- The potential role of the thymus in immunotherapies for acute myeloid leukemia.Frontiers in immunology · 2023Review
- Are aged pTreg cells "the more the better"?Aging · 2022Article
- Central tolerance is impaired in the middle-aged thymic environment.Aging cell · 2022Article
- Accumulation of pTreg cells is detrimental in late-onset (aged) mouse model of multiple sclerosis.Aging cell · 2022Article
- Review
- Immunosenescence, aging and successful aging.Frontiers in immunology · 2022Review
- Role of T Regulatory Cells and Myeloid-Derived Suppressor Cells in COVID-19.Journal of immunology research · 2022Review
- How Immunosenescence and Inflammaging May Contribute to Hyperinflammatory Syndrome in COVID-19.International journal of molecular sciences · 2021Review
- Thymic atrophy creates holes in Treg-mediated immuno-regulation via impairment of an antigen-specific clone.Immunology · 2021Article
- Review
- Review
- Age-Related Changes in Thymic Central Tolerance.Frontiers in immunology · 2021Review
- Thymic rejuvenation via FOXN1-reprogrammed embryonic fibroblasts (FREFs) to counteract age-related inflammation.JCI insight · 2020Article
- Nucleic Acid-Based Approaches for Tumor Therapy.Cells · 2020Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Postnatal thymic epithelial cell (TEC) homeostatic defect- or natural aging-induced thymic atrophy results in a decline in central T-cell tolerance establishment, which is constituted by thymocyte negative selection and cluster of differentiation (CD) 4+ thymic regulatory T (tTreg) cell generation. Emerging evidence shows this decline mainly results from defects in negative selection, but there is insufficient evidence regarding whether tTreg cell generation is also impaired. We mechanistically studied tTreg cell generation in the atrophied thymus by utilizing both postnatal TEC-defective (resulting from FoxN1-floxed conditional knockout [cKO]) and naturally aged mouse models. We found that the capacity of tTreg cell generation was not impaired compared to CD4+ thymic conventional T cells, suggesting thymic atrophy positively influences tTreg cell generation. This is potentially attributed to decreased T cell receptor (TCR) signaling strength due to inefficiency in promiscuous expression of self-antigens or presenting a neo-self-antigen by medullary TECs, displaying decreased negative selection-related marker genes (Nur77 and CD5high) in CD4 single positive (SP) thymocytes. Our results provide evidence that the atrophied thymus attempts to balance the defective negative selection by enhancing tTreg cell generation to maintain central T-cell tolerance in the elderly. Once the balance is broken, age-related diseases could take place.
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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.