ArticleNature medicine2012
Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity.
Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 221 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
221 citing papers in PubMed, 1 synthesis or guideline pooled it, 348 citations in OpenAlex.
- Immunosenescence: A systems-level overview of immune cell biology and strategies for improving vaccine responses.Experimental gerontology · 2019Pooled it
- CD8Science China. Life sciences · 2026Review
- Targeting immunosenescence in lung diseases: mechanistic insights and clinical interventions.BMC medicine · 2026Review
- DUSP6 ablation restores CAR T-cell fitness impaired by tumor CD58 loss through invigoration of AP-1 signaling.Signal transduction and targeted therapy · 2026Article
- Engineering Immune Cell to Counteract Aging and Aging-Associated Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Age-related thymic involution: Mechanistic insights and rejuvenating approaches to restore immune function.Science advances · 2026Review
- Application of the miRNAs as biomarkers and therapeutic strategies in periodontal inflammation.Frontiers in pharmacology · 2026Review
- Shaping the founders: naïve CD4 T cell heterogeneity in people with HIV-1 or HIV-2.Frontiers in immunology · 2026Article
- Molecular Mechanisms Behind Organ-Related Aging and Regulatory Effects of Natural Therapeutics.Cell biochemistry and biophysics · 2025Review
- Review
- Germinal center immune dynamics: challenges for effective vaccination in the elderly.Immunotherapy · 2025Review
- Differential effects of young and old hematopoietic stem cell niches on bone marrow-derived dendritic cells.Immunity & ageing : I & A · 2025Article
- An in-depth understanding of the role and mechanisms of T cells in immune organ aging and age-related diseases.Science China. Life sciences · 2025Review
- Enhancing vaccine effectiveness in the elderly to counter antibiotic resistance: The potential of adjuvants via pattern recognition receptors.Human vaccines & immunotherapeutics · 2024Review
- EphA-Mediated Regulation of Stomatin Expression in Prostate Cancer Cells.Cancer medicine · 2024Article
- A high-resolution map of functional miR-181 response elements in the thymus reveals the role of coding sequence targeting and an alternative seed match.Nucleic acids research · 2024Article
- Review
- Review
- Regulatory RNAs in immunosenescence.Immunity, inflammation and disease · 2024Review
- Accelarated immune ageing is associated with COVID-19 disease severity.Immunity & ageing : I & A · 2024Article
161 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
The ability of the human immune system to respond to vaccination declines with age. We identified an age-associated defect in T cell receptor (TCR)-induced extracellular signal-regulated kinase (ERK) phosphorylation in naive CD4(+) T cells, whereas other signals, such as ζ chain-associated protein kinase 70 (ZAP70) and phospholipase C-γ1 phosphorylation, were not impaired. The defective ERK signaling was caused by the dual specific phosphatase 6 (DUSP6), whose protein expression increased with age due to a decline in repression by miR-181a. Reconstitution of miR-181a lowered DUSP6 expression in naive CD4(+) T cells in elderly individuals. DUSP6 repression using miR-181a or specific siRNA and DUSP6 inhibition by the allosteric inhibitor (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one improved CD4(+) T cell responses, as seen by increased expression of activation markers, improved proliferation and supported preferential T helper type 1 cell differentiation. DUSP6 is a potential intervention target for restoring T cell responses in the elderly, which may augment the effectiveness of vaccination.
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What OpenQuestion holds
Registered trials
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.