ArticleNPJ aging and mechanisms of disease2021
The GSK3β-β-catenin-TCF1 pathway improves naive T cell activation in old adults by upregulating miR-181a.
Article in NPJ aging and mechanisms of disease, 2021. 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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Who cites it
13 citing papers in PubMed, 14 citations in OpenAlex.
- Control of naive T cell reactivity and peripheral tolerance by ascorbate and TET activity.Science advances · 2026Article
- GSK-3 regulates CD4-CD8 cooperation for super-armed CD8+ cytolytic T cells in immunotherapy against tumors.Signal transduction and targeted therapy · 2026Article
- Wnt Signaling Downregulation Mediates T Cell Apoptosis Following OKT3-Induced T Cell Activation in Preclinical Models.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- TCF1bioRxiv : the preprint server for biology · 2026Article
- Comment on: Glycogen synthase kinase 3 controls T-cell exhaustion by regulating NFAT activation.Cellular & molecular immunology · 2025Article
- The functions of immune system-derived miRNAs in cardiovascular diseases.Non-coding RNA research · 2025Review
- PRR enhances anti-tumor immunity and suppresses colitis by promoting the development and survival of naive T and iNKT cells.Frontiers in immunology · 2025Article
- T cell fate decisions during memory cell generation with aging.Seminars in immunology · 2023Review
- Hallmarks of the aging T-cell system.The FEBS journal · 2021Review
- Understanding T cell aging to improve anti-viral immunity.Current opinion in virology · 2021Review
- Article
- miR-181a-regulated pathways in T-cell differentiation and aging.Immunity & ageing : I & A · 2021Review
- MicroRNAs as Factors in Bidirectional Crosstalk Between Mitochondria and the Nucleus During Cellular Senescence.Frontiers in physiology · 2021Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
MicroRNAs play an important role in the regulation of T cell development, activation, and differentiation. One of the most abundant microRNAs in lymphocytes is miR-181a, which controls T cell receptor (TCR) activation thresholds in thymic selection as well as in peripheral T cell responses. We previously found that miR-181a levels decline in T cells in the elderly. In this study, we identified TCF1 as a transcriptional regulator of pri-miR-181a. A decline in TCF1 levels in old individuals accounted for the reduced miR-181a expression impairing TCR signaling. Inhibition of GSK3ß restored expression of miR-181a by inducing TCF1 in T cells from old adults. GSK3ß inhibition enhanced TCR signaling to increase downstream expression of activation markers and production of IL-2. The effect involved the upregulation of miR-181a and the inhibition of DUSP6 expression. Thus, inhibition of GSK3ß can restore responses of old T cells by inducing miR-181a expression through TCF1.
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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.