ArticleJCI insight2025
The inflammaging microenvironment induces dysfunctional rewiring of Tfh cell differentiation.
Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Targeting T follicular helper cells for lifelong health.Nature reviews. Drug discovery · 2026Review
- Post-vaccination expansion of extrafollicular Th10 and regulatory Tfr cells distinguishes strong from weak influenza vaccine responses in older adults.medRxiv : the preprint server for health sciences · 2026Article
- Highlights of 2025: advances in germinal centers.Immunology and cell biology · 2026Review
- Aging restricts maturation of CXCL13bioRxiv : the preprint server for biology · 2026Article
- Stability and progressive differentiation of TNature immunology · 2026Article
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
Humoral immunity is orchestrated by follicular helper T (Tfh) cells, which promote cognate B cells to produce high-affinity, protective antibodies. In aged individuals, humoral immunity after vaccination is diminished despite the presence of Tfh cells, suggesting defects after initial Tfh cell formation. In this study, we utilized both murine and human systems to investigate how aging alters Tfh cell differentiation after influenza vaccination. We found that young Tfh cells underwent progressive differentiation after influenza vaccination, culminating in clonal expansion of effector-like cells in both draining lymph nodes and blood. In aging, early stages of Tfh cell development occurred normally. However, aging rewired the later stages of development in Tfh cells, resulting in a transcriptional program reflective of cellular senescence, sustained pro-inflammatory cytokine production, and metabolic reprogramming. We investigated the extent to which this rewiring of aged Tfh cells is due to the age-associated inflammatory ("inflammaging") microenvironment and found that this setting was sufficient to both block the transition of Tfh cells to a post-effector resting state and skew Tfh cells toward the age-rewired state. Together, these data suggest that aging dampens humoral immunity by cytokine-mediated rewiring of late effector Tfh cell differentiation into an activated, yet less functional, cellular state.
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Registered trials
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