ArticleAging and disease2012
Age-Related Disruption of Steady-State Thymic Medulla Provokes Autoimmune Phenotype via Perturbing Negative Selection.
Article in Aging and disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
The trial behind it
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
29 citing papers in PubMed, 41 citations in OpenAlex.
- Immunoporosis: The hidden link between aging immune cells and bone fragility.Journal of orthopaedic translation · 2025Review
- Endogenous thymic regeneration: restoring T cell production following injury.Nature reviews. Immunology · 2025Review
- Paracrine FGF21 dynamically modulates mTOR signaling to regulate thymus function across the lifespan.Nature aging · 2025Article
- Foxn1 overexpression promotes thymic epithelial progenitor cell proliferation and mTEC maintenance, but does not prevent thymic involution.Development (Cambridge, England) · 2023Article
- Differences in Age-Related Changes in the Thymus in Rats Developmentally Exposed to Endocrine Disrupter Dichlorodiphenyltrichloroethane.Bulletin of experimental biology and medicine · 2023Article
- Review
- Thymic atrophy creates holes in Treg-mediated immuno-regulation via impairment of an antigen-specific clone.Immunology · 2021Article
- Review
- Dynamics of thymus function and T cell receptor repertoire breadth in health and disease.Seminars in immunopathology · 2021Review
- The contribution of thymic tolerance to central nervous system autoimmunity.Seminars in immunopathology · 2021Review
- Thymic rejuvenation via FOXN1-reprogrammed embryonic fibroblasts (FREFs) to counteract age-related inflammation.JCI insight · 2020Article
- Postnatal Involution and Counter-Involution of the Thymus.Frontiers in immunology · 2020Review
- Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging.Immunity & ageing : I & A · 2020Review
- Role of Regulatory T cells in Atorvastatin Induced Absorption of Chronic Subdural Hematoma in Rats.Aging and disease · 2019Article
- Th1 Biased Progressive Autoimmunity in AgedAging and disease · 2019Article
- Dealing with the adaptive immune system during de novo evolution of genes from intergenic sequences.BMC evolutionary biology · 2018Article
- Extracellular vesicles extracted from young donor serum attenuate inflammaging via partially rejuvenating aged T-cell immunotolerance.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Twenty Years of AIRE.Frontiers in immunology · 2018Review
- Capacity of tTreg generation is not impaired in the atrophied thymus.PLoS biology · 2017Article
- Gut dysbiosis breaks immunological tolerance toward the central nervous system during young adulthood.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The hymic medulla plays an essential role in the generation of central tolerance by eliminating self-reactive T-cell clones through thymic negative selection and developing natural regulatory T cells. Age-related FoxN1 decline induces disruption of medullary thymic epithelial cells (mTECs). However, it is unknown whether this perturbs central tolerance to increase autoimmune predisposition in the elderly. Using a loxP-floxed-FoxN1 (FoxN1(flox)) mouse model, which exhibits a spontaneous ubiquitous deletion of FoxN1 with age to accelerate thymic aging, we investigated whether disruption of steady-state thymic medulla results in an increase of autoimmune-prone associated with age. We demonstrated age-associated ubiquitous loss of FoxN1(flox)-formed two-dimensional thymic epithelial cysts were primarily located in the medulla. This resulted in disruption of thymic medullary steady state, with evidence of perturbed negative selection, including reduced expression of the autoimmune regulator (Aire) gene and disrupted accumulation of thymic dendritic cells in the medulla, which are required for negative selection. These provoke autoimmune phenotypes, including increased inflammatory cell infiltration in multiple organs in these mice. This finding in an animal model provides a mechanistic explanation of increased susceptibility to autoimmunity in aged humans, although they may not show clinic manifestations without induction.
Indexed as
Identifiers
22724083PMC3375081W1720514029What OpenQuestion holds
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.