ArticleAging cell2016
Interleukin-21 administration to aged mice rejuvenates their peripheral T-cell pool by triggering de novo thymopoiesis.
Article in Aging cell, 2016. 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, 37 citations in OpenAlex.
- Age-related thymic involution: Mechanistic insights and rejuvenating approaches to restore immune function.Science advances · 2026Review
- Research advances and application prospects of CAR-T therapy in the treatment of age-related diseases.Frontiers in immunology · 2026Review
- Network-orchestrated regulation of thymic dysfunction and restoration.Frontiers in immunology · 2026Review
- Immunosenescence and organoids: pathophysiology and therapeutic opportunities.Immunity & ageing : I & A · 2025Review
- Endogenous thymic regeneration: restoring T cell production following injury.Nature reviews. Immunology · 2025Review
- The Role of Senescence, its Therapeutic Relevance and Clinical Implications in the Tumor Microenvironment.Theranostics · 2025Review
- Strategies for Reducing Toxicity and Enhancing Efficacy of Chimeric Antigen Receptor T Cell Therapy in Hematological Malignancies.International journal of molecular sciences · 2023Review
- Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases.Signal transduction and targeted therapy · 2023Review
- The potential role of the thymus in immunotherapies for acute myeloid leukemia.Frontiers in immunology · 2023Review
- Cushing syndrome and glucocorticoids: T-cell lymphopenia, apoptosis, and rescue by IL-21.The Journal of allergy and clinical immunology · 2022Article
- DUSP5 promotes osteogenic differentiation through SCP1/2-dependent phosphorylation of SMAD1.Stem cells (Dayton, Ohio) · 2021Article
- Recent Advancements in Regenerative Approaches for Thymus Rejuvenation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- T cell regeneration after immunological injury.Nature reviews. Immunology · 2021Review
- Dynamics of thymus function and T cell receptor repertoire breadth in health and disease.Seminars in immunopathology · 2021Review
- Optimizing T Cell-Based Therapy for Glioblastoma.Frontiers in immunology · 2021Review
- Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy.Frontiers in immunology · 2021Review
- TCR-T Immunotherapy: The Challenges and Solutions.Frontiers in oncology · 2021Review
- A Novel Sulfonyl-Based Small Molecule Exhibiting Anti-cancer Properties.Frontiers in pharmacology · 2020Article
- Complex and Multilayered Role of IL-21 Signaling during Thymic Development.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- The Evolving Role of CD8International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The vaccination efficacy in the elderly is significantly reduced compared to younger populations due to thymic involution and age-related intrinsic changes affecting their naïve T-cell compartment. Interleukin (IL)-21 was recently shown to display thymostimulatory properties. Therefore, we hypothesized that its administration to ageing hosts may improve T-cell output and thus restore a competent peripheral T-cell compartment. Indeed, an increase in the production of recent thymic emigrants (RTEs) attributable to intrathymic expansion of early thymic progenitors (ETPs), double-negative (DN), and double-positive (DP) thymocytes as well as thymic epithelial cell (TEC) was observed in recombinant (r)IL-21-treated aged mice. In sharp contrast, no alterations in the frequency of bone marrow (BM)-derived progenitors were detected following rIL-21 administration. Enhanced production of naïve T cells improved the T-cell receptor (TCR) repertoire diversity and re-established a pool of T cells exhibiting higher levels of miR-181a and diminished amounts of the TCR-inhibiting phosphatases SHP-2 and DUSP5/6. As a result, stimulation of T cells derived from rIL-21-treated aged mice displayed enhanced activation of Lck, ZAP-70, and ERK, which ultimately boosted their IL-2 production, CD25 expression, and proliferation capabilities in comparison with T cells derived from control aged mice. Consequently, aged rIL-21-treated mice vaccinated using a tyrosinase-related protein 2 (Trp2)-derived peptide exhibited a substantial delay in B16 tumor growth and improved survival. The results of this study highlight the immunorestorative function of rIL-21 paving its use as a strategy for the re-establishment of effective immunity in the elderly.
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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.