Declining expression of a single epithelial cell‐autonomous gene accelerates age‐related thymic involution
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Summary: Age‐related thymic involution may be triggered by gene expression changes in lymphohematopoietic and/or nonhematopoietic thymic epithelial cells (TECs). The role of epithelial cell‐autonomous gene FoxN1 may be involved in the process, but it is still a puzzle because of the shortage of evidence from gradual loss‐of‐function and exogenous gain‐of‐function studies. Using our recently generated loxP‐floxed‐FoxN1(fx) mouse carrying the ubiquitous CreER T (uCreER T) transgene with a low dose of spontaneous activation, which causes gradual FoxN1 deletion with age, we found that the uCreER T‐fx/fx mice showed an accelerated age‐related thymic involution owing to progressive loss of FoxN1+ TECs. The thymic aging phenotypes were clearly observable as early as at 3–6 months of age, resembling the naturally aged (18–22‐month‐old) murine thymus. By intrathymically supplying aged wild‐type mice with exogenous FoxN1‐cDNA, thymic involution and defective peripheral CD4+ T‐cell function could be partially rescued. The results support the notion that decline of a single epithelial cell‐autonomous gene FoxN1 levels with age causes primary deterioration in TECs followed by impairment of the total postnatal thymic microenvironment, and potentially triggers age‐related thymic involution in mice.
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Injection of a plasmid vector carrying FOXN1-cDNA into the thymus of elderly mice causes a partial rescue in the size of the thymus and the number of thymocytes.
“Similarly, a report has shown that the injection of a plasmid vector carrying FOXN1-cDNA into the thymus of elderly mice would cause a partial rescue in the size of the thymus and the number of thymocytes [172].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [172]
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Self-citation
- Authors
- Sun, L., Guo, J., Brown, R., Amagai, T., Zhao, Y., & Su, D.
- Affiliations
- The University of Texas Health Science Center at Tyler (US)
- Meiji University of Integrative Medicine (JP)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Su, Dong‐Ming
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2010-05-18
- Volume
- 9
- Issue
- 3
- Pages
- 347-357
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC2894280
- OpenAlex
- W1524089769
- Cited by
- 83
- References
- 45
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 8 · 2020: 10 · 2019: 5 · 2018: 1 · 2017: 4 · 2016: 7 · 2015: 8 · 2014: 3 · 2013: 4 · 2012: 8
- FWCI
- 2.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Massachusetts General Hospital
- National Institutes of Health
- National Institute on Aging (R21AG031880)
- National Institute of Allergy and Infectious Diseases (R01AI081995, R21AI079747)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Neurology › Myasthenia Gravis and Thymoma
- Keywords
- thymic involution, Foxn1, thymic epithelial cells, thymic aging, thymic microenvironment, thymus regeneration
- MeSH terms
- Aging, Animals, Epithelial Cells, Mice, Nude, Mice, Transgenic, Organ Size, Thymus Gland, CD4-Positive T-Lymphocytes, Down-Regulation, Cell Proliferation, Mice, Forkhead Transcription Factors
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