ArticleProceedings of the National Academy of Sciences of the United States of America2024
Restoration of LAMP2A expression in old mice leads to changes in the T cell compartment that support improved immune function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Decline of chaperone-mediated autophagy in aging impairs macrophage clearance of senescent cells.Nature aging · 2026Article
- Chaperone-mediated autophagy in physiological homeostasis, disease and ageing.Nature reviews. Molecular cell biology · 2026Review
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- Intervening in aging and related diseases with gene therapy techniques.Cell reports. Medicine · 2026Review
- Chaperone-mediated autophagy is a tumor-suppressive mechanism in hepatocellular carcinoma.Cell reports · 2026Article
- Chaperone-mediated autophagy is required for regulatory T cell function.Nature communications · 2026Article
- Critical Roles and Molecular Mechanisms of Chaperone-Mediated Autophagy in Infections.International journal of molecular sciences · 2026Review
- Unraveling the intersection of aging and Parkinson's disease: a collaborative roadmap for advancing research models.NPJ Parkinson's disease · 2026Review
- Dysfunction of lipid metabolism and lysosomal capacity: at the core of microglial aging?Frontiers in aging neuroscience · 2026Review
- Targeting chaperone-mediated autophagy inhibits properties of glioblastoma stem cells and restores anti-tumor immunity.Nature communications · 2025Article
- Chaperone-mediated autophagy regulates neuronal activity by sex-specific remodelling of the synaptic proteome.Nature cell biology · 2025Article
- Metabolic regulation of immunological aging.Nature aging · 2025Review
- Sex-specific and cell-type-specific changes in chaperone-mediated autophagy across tissues during aging.Nature aging · 2025Article
- The link between ferroptosis and autophagy in myocardial ischemia/reperfusion injury: new directions for therapy.Journal of cardiovascular translational research · 2025Review
- Bidirectional crosstalk between the bone extracellular matrix and lysosomes in bone remodeling and osteoporosis.Frontiers in endocrinology · 2025Review
- Tracking Chaperone-Mediated Autophagy Flux with a pH-Resistant Fluorescent Reporter.International journal of molecular sciences · 2024Article
- Restoration of LAMP2A expression in old mice leads to changes in the T cell compartment that support improved immune function.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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10 authors.
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Abstract
Chaperone-mediated autophagy (CMA) is a selective form of autophagy that contributes to the maintenance of cellular homeostasis. CMA activity declines with age in most tissues and systems, including the immune system, due to a reduction in levels of lysosome-associated membrane protein type 2A (LAMP2A), an essential CMA component. In this study, we show that overexpressing a copy of hLAMP2A within T cells since middle-age can prevent some of their age-associated loss of function. Our data support the idea that preserving LAMP2A expression with age through genetic means leads to enhanced proliferative responses, decreased number of regulatory T cell populations, and down-regulated expression of inhibitory receptors by T cells. During aging, elevated numbers of these immunosuppressive T cell populations significantly contribute to the age-associated downregulation of T cell responses. Using comparative proteomics, we confirm that preservation of CMA activity in old mice prevents age-related changes in both the resting and the activated T cell proteome. We also explore the effect of using first-in-class small molecule activators of CMA and demonstrate improved T cell response upon their administration to old mice. We conclude that sustaining CMA activity constitutes a potentially viable therapeutic approach to improving T cell function with age.
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