ArticleNature aging2025
Heme and iron toxicity in the aged spleen impairs T cell immunity through iron deprivation.
Article in Nature aging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Transmetallic biomimetic Hydrogel implants restore osteogenesis-angiogenesis coupling via Fe/Co ionic microenvironment remodeling for enhancing osteoporotic fracture healing.Bioactive materials · 2027Article
- Cardiac-targeting peptide-modified Prussian blue nanozymes loaded with Astragaloside IV for efficient ICI-myocarditis therapy.Materials today. Bio · 2026Article
- GW9508-Induced Activation of GPR40 in Thymic Epithelial Cells: A Therapeutic Strategy to Delay Thymic Aging.Aging cell · 2026Article
- CIITA/PRMT5 promote CD4BMC medicine · 2026Article
- Regulation of T Cell Senescence in Health and Diseases.Immune network · 2026Review
- T-Cell Immunosenescence in Systemic Lupus Erythematosus: Molecular Mechanisms and Therapeutic Perspectives.Clinical reviews in allergy & immunology · 2026Review
- Immune Aging as a Failure of Programmed Cell Death Coordination.International journal of molecular sciences · 2026Review
- Article
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Authors and funding
8 authors.
Funding
Abstract
Mechanisms of T cell aging involve cell-intrinsic alterations and interactions with immune and stromal cells. Here we found that splenic T cells exhibit greater functional decline than lymph node T cells within the same aged mouse, prompting investigation into how the aged spleen contributes to T cell aging. Proteomic analysis revealed increased expression of heme detoxification in aged spleen-derived lymphocytes. Exposure to the heme- and iron-rich aged splenic microenvironment induced aging phenotypes in young T cells, including reduced proliferation and CD39 upregulation. T cells survived this hostile niche by maintaining a low labile iron pool, at least in part, via IRP2 downregulation to resist ferroptosis but failed to induce sufficient iron uptake for activation. Iron supplementation enhanced antigen-specific T cell responses in aged mice. This study identifies the aged spleen as a source of hemolytic signals that systemically impair T cell function, underscoring a trade-off between T cell survival and function and implicating iron metabolism in immune aging.
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