ArticleFrontiers in immunology2023
Acute irradiation causes a long-term disturbance in the heterogeneity and gene expression profile of medullary thymic epithelial cells.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 14 citations in OpenAlex.
- The Impact of NEAT1 on Inflammatory Responses and Processes in Arthropathic Diseases: Latest Findings and Perspectives.Biochemical genetics · 2026Review
- SenFlag gene signature identifies senescent cells in mouse and human tissues through a conserved core transcriptional program.The EMBO journal · 2026Article
- Immune reset: what do we learn from bone marrow transplantation.Medical review (2021) · 2026Review
- From Development to Aging: Dynamic Roles of the Thymic Medulla in T Cell Biology.Immunological reviews · 2026Review
- Proteasome inhibition promotes Foxn1 expression in thymic epithelial cells and induces thymic regeneration in mice.Cell death and differentiation · 2026Article
- Radioresistant intrathymic stem cells: retrospective analysis and concept of the role in thymic oncogenesis and post-irradiation regeneration.Frontiers in immunology · 2026Review
- Mechanism and intervention strategy of thymus atrophy in cancer immunotherapy.American journal of cancer research · 2026Review
- Whole-Thorax Irradiation Induces Persistent T Cell Clonal Dysregulation in Pediatric Rhesus Macaques.Radiation research · 2025Article
- Sterile production of interferons in the thymus.Journal of immunology (Baltimore, Md. : 1950) · 2025Review
- Endogenous thymic regeneration: restoring T cell production following injury.Nature reviews. Immunology · 2025Review
- Generation and repair of thymic epithelial cells.The Journal of experimental medicine · 2024Review
- Age-related epithelial defects limit thymic function and regeneration.Nature immunology · 2024Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The thymus has the ability to regenerate from acute injury caused by radiation, infection, and stressors. In addition to thymocytes, thymic epithelial cells in the medulla (mTECs), which are crucial for T cell self-tolerance by ectopically expressing and presenting thousands of tissue-specific antigens (TSAs), are damaged by these insults and recover thereafter. However, given recent discoveries on the high heterogeneity of mTECs, it remains to be determined whether the frequency and properties of mTEC subsets are restored during thymic recovery from radiation damage. Here we demonstrate that acute total body irradiation with a sublethal dose induces aftereffects on heterogeneity and gene expression of mTECs. Single-cell RNA-sequencing (scRNA-seq) analysis showed that irradiation reduces the frequency of mTECs expressing AIRE, which is a critical regulator of TSA expression, 15 days after irradiation. In contrast, transit-amplifying mTECs (TA-mTECs), which are progenitors of AIRE-expressing mTECs, and Ccl21a-expressing mTECs, were less affected. Interestingly, a detailed analysis of scRNA-seq data suggested that the proportion of a unique mTEC cluster expressing Ccl25 and a high level of TSAs was severely decreased by irradiation. In sum, we propose that the effects of acute irradiation disrupt the heterogeneity and properties of mTECs over an extended period, which potentially leads to an impairment of thymic T cell selection.
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