ArticleAging cell2021
Ageing promotes early T follicular helper cell differentiation by modulating expression of RBPJ.
Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Targeting T follicular helper cells for lifelong health.Nature reviews. Drug discovery · 2026Review
- A unified network systems approach uncovers a core program underlying T follicular helper cell differentiation.Nature communications · 2026Article
- Adenosine deaminase co-immunization reverses age-associated immunosenescence by restoring germinal center T follicular helper cell function.bioRxiv : the preprint server for biology · 2026Article
- Aging restricts maturation of CXCL13bioRxiv : the preprint server for biology · 2026Article
- Review
- Cytotoxic CD4Frontiers in immunology · 2025Article
- Benefit delayed immunosenescence by regulating CD4Aging cell · 2024Review
- The expression of RBPJ and its potential role in rheumatoid arthritis.BMC genomics · 2024Article
- The aged microenvironment impairs BCL6 and CD40L induction in CD4Aging cell · 2024Article
- Adaptive immunity and atherosclerosis: aging at its crossroads.Frontiers in immunology · 2024Review
- Systemic immunometabolism and responses to vaccines: insights from T and B cell perspectives.International immunology · 2023Review
- Accumulation of immune-suppressive CD4 + T cells in aging - tempering inflammaging at the expense of immunity.Seminars in immunology · 2023Review
- Spatial dysregulation of T follicular helper cells impairs vaccine responses in aging.Nature immunology · 2023Article
- Molecular Markers of Blood Cell Populations Can Help Estimate Aging of the Immune System.International journal of molecular sciences · 2023Review
- The memory B cell response to influenza vaccination is impaired in older persons.Cell reports · 2022Article
- Follicular T cells optimize the germinal center response to SARS-CoV-2 protein vaccination in mice.Cell reports · 2022Article
- Mechanisms underpinning poor antibody responses to vaccines in ageing.Immunology letters · 2022Review
- The dark side of Tregs during aging.Frontiers in immunology · 2022Review
- Human immune diversity: from evolution to modernity.Nature immunology · 2021Review
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Ageing profoundly changes our immune system and is thought to be a driving factor in the morbidity and mortality associated with infectious disease in older people. We have previously shown that the impaired immunity to vaccination that occurs in aged individuals is partly attributed to the effect of age on T follicular helper (Tfh) cell formation. In this study, we examined how age intrinsically affects Tfh cell formation in both mice and humans. We show increased formation of Tfh precursors (pre-Tfh) but no associated increase in germinal centre (GC)-Tfh cells in aged mice, suggesting age-driven promotion of only early Tfh cell differentiation. Mechanistically, we show that ageing alters TCR signalling which drives expression of the Notch-associated transcription factor, RBPJ. Genetic or chemical modulation of RBPJ or Notch rescues this age-associated early Tfh cell differentiation, and increased intrinsic Notch activity recapitulates this phenomenon in younger mice. Our data offer mechanistic insight into the age-induced changes in T-cell activation that affects the differentiation and ultimately the function of effector T cells.
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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.