ArticleJCI insight2024
PREX1 improves homeostatic proliferation to maintain a naive CD4+ T cell compartment in older age.
Article in JCI insight, 2024. 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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The trial behind it
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Who cites it
8 citing papers in PubMed, 7 citations in OpenAlex.
- The ageing immune system as a driver of systemic ageing.Nature reviews. Immunology · 2026Review
- Diversity, Equality, and Inclusion in the naïve T Cell Receptor Repertoire.Immunological reviews · 2026Review
- Multidimensional dissection of shared genetic susceptibility in ulcerative colitis and colorectal cancer: novel insights from integrative single-cell and multi-omics analysis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- B cells drive CD4 T cell immunosenescence and age-associated health decline.Science immunology · 2026Article
- Comprehensive bulk and single-cell RNA sequencing uncovers senescence-associated biomarkers in therapeutic mesenchymal stem cells.Scientific reports · 2025Article
- Polymorphic tandem repeats influence cell type-specific gene expression across the human immune landscape.bioRxiv : the preprint server for biology · 2025Article
- Exome sequencing identifies novel genes associated with cerebellar volume and microstructure.Communications biology · 2025Article
- P-Rex1 controls phagocytosis and the killing of bacteria by murine neutrophils independently of its catalytic activity.Frontiers in immunology · 2025Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The human adult immune system maintains normal T cell counts and compensates for T cell loss throughout life, mainly through peripheral homeostatic proliferation after the ability of the thymus to generate new T cells has rapidly declined at adolescence. This process is mainly driven by STAT5-activating cytokines, most importantly IL-7, and is very effective in maintaining a large naive CD4+ T cell compartment into older age. Here, we describe that naive CD4+ T cells undergo adaptations to optimize IL-7 responses by upregulating the guanine-nucleotide exchange factor PREX1 in older age. PREX1 promotes nuclear translocation of phosphorylated STAT5, thereby supporting homeostatic proliferation in response to IL-7. Through the same mechanism, increased expression of PREX1 also biases naive cells to differentiate into effector T cells. These findings are consistent with the concept that primarily beneficial adaptations during aging, i.e., improved homeostasis, account for unfavorable functions of the aged immune system, in this case biased differentiation.
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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.